INTRODUCTION: There is considerable uncertainty with respect to predicting the liver disease status of African American (AA) patients with Hepatitis C seen in the current era of highly effective direct acting anti-virals (DAA). This uncertainty is due to the complex interplay between the identification of patients early in their disease progression by screening, the fact that many AA patients failed earlier interferon based therapy, duration of the HCV viremia in AA patients, the possible variation In disease course in AA as compared to other races, and potential early mortality of AA patients due to liver disease. Understanding the evolution of HCV infection as defined by comparing previous and current patient populations provides information relevant to both therapeutic and health costs decisions. METHODS: We selected patients from a 24 month period between 2002 and 2003 (Epoch 1; n = 414) to compare with patients seen in the same GI clinic between 2012 and 2013 (Epoch 2; n=405). Epoch 1 was the beginning of the peg-interferon and ribavirin treatment era and Epoch 2 reflects the patient population seen when DAA therapy was first available. RESULTS: Epoch 2 patients were older (59.7 vs 50.3 years) with a similar gender distribution (55% vs 59% male). Consistent with the change in clinic demographics, more AA patients were seen in Epoch 2 (89%) as compared to Epoch 1 (77%). There was no significant difference between hepatic fibrosis as assessed by APRI (1.1 vs 0.9) or FIB-4 (2.4 vs 2.6) but there was an increase in intermediate degree of fibrosis as defined by liver biopsy. The majority of Epoch 2 patients were still naïve to treatment (96% Epoch 1 vs 61% Epoch 2) and a similar proportion had cirrhosis (15% Epoch 1 vs 17% Epoch 2) at the time of first visit in the different time periods. CONCLUSIONS: The patients in Epoch 2 from this urban GI referral clinic are older and the majority of them had not been treated or had not responded to treatment. This age demographic continues to reflect patients who were likely infected during the 1960's-1980's which is when HCV infection became widespread. Epoch 2 patients also do not have more advanced liver disease as defined either by significant fibrosis or cirrhosis as compared to Epoch 1. Possible explanations include that Epoch 2 patients' disease was detected earlier by surveillance, progressed very slowly to advanced liver disease, or had a high mortality that resulted in a decline in patients with advanced disease. The role of access to therapy in patients not treated remains to be determined and the increased effectiveness of DAA are predicted to increase the number of AA patients seeking and accepting treatment.
The Fontan circulation alters a patient’s physiology and imparts long-term risks related to chronically elevated systemic venous pressure. An increasing number of patients with Fontan physiology are surviving into adulthood and are at risk of hepatic sequalae. The ideal timeline and method of hepatic surveillance in the Fontan population remains to be defined. In this case, the patient was diagnosed with hepatocellular carcinoma more than 20 years after undergoing the Fontan procedure and was a candidate for combined heart-liver transplant. That her disease progressed prior to organ availability supports the argument for hepatic surveillance in this population.
Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. The patient had been treated with ipilimumab and nivolumab in the past two months. The infectious workup was inconclusive. Colonoscopy demonstrated severe colitis, and biopsies were consistent with colitis. Combination chemotherapy was stopped. The patient was treated with intravenous and oral steroids, and her symptoms improved. A combination of ipilimumab and nivolumab increases the chance of immune-mediated colitis, and steroids should be started promptly to avoid complications such as bowel perforation and toxic megacolon.
The anticarcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’, with users more likely diagnosed with early rather than late stage cancer. The association between prior statin use and colorectal cancer (CRC) stage at diagnosis in the Women's Health Initiative (WHI) was investigated. The study population included 132,322 post-menopausal women, among which there were 2,628 pathologically confirmed cases of in situ (3.3%), localized (43.6%), regional (40.4%) and distant (12.7%) stage CRC, after an average of 13.9 (SD=4.7) years of follow-up. To reduce the possibility of detection bias among women more likely to be prescribed statins, women who did not report a mammogram within 5 years of study entry and who had no health insurance or medical care provider (n=28,237) were excluded from the study. Stage was coded using SEER criteria into early ( in situ and local) vs. late (regional and distant) stage disease. Hazards ratios (HR) and 95% confidence intervals (CIs) evaluating the association between statin use and diagnosis of late-stage CRC both at baseline and in a time-dependent manner were computed from multivariable-adjusted Cox proportional hazards analyses. In the multivariable time-dependent analysis, there was a lower hazard of late stage CRC among users of lipophilic statins compared with non-users (HR=0.80, 95% CI 0.66-0.98, P=0.029) and a marginally lower hazard of late stage CRC among users of lipophilic vs. hydrophilic statins (HR=0.70, 95% CI 0.49-1.01, P=0.058). The use of lipophilic statins was associated with a reduction in the proportion of CRC cases that were late stage at the time of diagnosis.
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