Hepatocellular carcinoma surveillance, early detection and survival in a privately insured US cohort

Background/AimsSemiannual hepatocellular carcinoma (HCC) surveillance is recommended in patients with cirrhosis; however, recent studies have raised questions over its utility. We investigated the impact of surveillance on early detection and survival in a nationally representative database.MethodsWe included patients with cirrhosis and HCC from the Optum database (2001‐2015) with >6 months of follow‐up between cirrhosis and HCC diagnoses. Surveillance adherence was defined as proportion of time covered (PTC), with each 6‐month period after abdominal imaging defined as ‘covered’. To determine the association between surveillance and mortality, we compared PTC between fatal and non‐fatal HCC.ResultsOf 1001 patients with cirrhosis and HCC, 256 died with median follow‐up 30 months. Median PTC by any imaging was greater in early‐stage vs late‐stage HCC (43.6% vs 37.4%, P = .003) and non‐fatal vs fatal HCC (40.8% vs 34.3%, P = .001). In multivariable analyses, each 10% increase in PTC was associated with increased early HCC detection (OR 1.07, 95% CI 1.01‐1.12) and decreased mortality (HR 0.95; 95% CI 0.90‐1.00). On subgroup analysis, PTC by CT/MRI was associated with early tumour detection and decreased mortality; however, PTC by ultrasound was only associated with early detection but not decreased mortality. These findings were robust across sensitivity analyses.ConclusionsIn a US cohort of privately insured HCC patients, PTC by any imaging modality was associated with increased early detection and decreased mortality. Continued evaluation of HCC surveillance strategies and effectiveness is warranted.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154974/1/liv14379_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154974/2/liv14379.pd

Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis

Aliment Pharmacol Ther 2010; 32: 1211–1221Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment.To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH.Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias.Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36–0.77, P  = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24–0.49, P  < 0.001) and ALT (WMD = 16.4, 95% CI 7.7–25.0, P  < 0.001), but not inflammation ( P  = 0.09) or fibrosis ( P  = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078–0.51, P  = 0.008). Metformin failed to improve any pooled outcome.Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79251/1/j.1365-2036.2010.04467.x.pd

Meta-analysis: re-treatment of genotype I hepatitis C nonresponders and relapsers after failing interferon and ribavirin combination therapy

Aliment Pharmacol Ther 2010; 32: 969–983The efficacy of re-treating genotype I hepatitis C virus (HCV) patients who failed combination therapy with interferon/pegylated interferon (PEG-IFN) and ribavirin remains unclear.To quantify sustained virological response (SVR) rates with different re-treatment regimens through meta-analysis of randomized controlled trials (RCTs).Randomized controlled trials of genotype I HCV treatment failure patients that compared currently available re-treatment regimens were selected. Two investigators independently extracted data on patient population, methods and results. The pooled relative risk of SVR for treatment regimens was computed using a random effects model.Eighteen RCTs were included. In nonresponders to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN combination therapy improved SVR compared with standard PEG-IFN combination therapy (RR = 1.49; 95% CI: 1.09–2.04), but SVR rates did not exceed 18% in most studies. In relapsers to standard interferon/ribavirin, re-treatment with high-dose PEG-IFN or prolonged CIFN improved SVR (RR = 1.57; 95% CI: 1.16–2.14) and achieved SVR rates of 43–69%.In genotype I HCV treatment failure patients who received combination therapy, re-treatment with high-dose PEG-IFN combination therapy is superior to re-treatment with standard combination therapy, although SVR rates are variable for nonresponders (≤18%) and relapsers (43–69%). Re-treatment may be appropriate for select patients, especially relapsers and individuals with bridging fibrosis or compensated cirrhosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79170/1/j.1365-2036.2010.04427.x.pd

in Utero Exposure to antiemetic and Risk of adult-Onset Colorectal Cancer

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s. METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 liveborn offspring). We reviewed prescribed medications from mothers\u27 medical records to identify those who received Bendectin during pregnancy. Diagnoses of CRC in adult (aged ≥18 years) offspring were ascertained by linkage with the California Cancer Registry. Cox proportional hazards models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact. RESULTS: Approximately 5% of offspring (n = 1014) were exposed in utero to Bendectin. Risk of CRC was higher in offspring exposed in utero (adjusted hazard ratio = 3.38, 95% confidence interval [CI] = 1.69 to 6.77) compared with unexposed offspring. Incidence rates of CRC were 30.8 (95% CI = 15.9 to 53.7) and 10.1 (95% CI = 7.9 to 12.8) per 100 000 in offspring exposed to Bendectin and unexposed, respectively. CONCLUSIONS: Higher risk of CRC in offspring exposed in utero may be driven by dicyclomine contained in the 3-part formulation of Bendectin used during the 1960s. Experimental studies are needed to clarify these findings and identify mechanisms of risk

Non-alcoholic fatty liver disease-related hepatocellular carcinoma

Non-alcoholic fatty liver disease (NAFLD), one of the most common causes of liver disease, is an increasingly common cause of hepatocellular carcinoma (HCC). Several demographic, clinical, and genetic factors contribute to HCC risk in NAFLD patients, which may inform risk stratification scores. Proven efficacious approaches to primary prevention approach in patients with non-viral liver disease remain an area of need. Semi-annual surveillance is associated with improved early tumor detection and reduced HCC-related mortality; however, patients with NAFLD have several challenges to effective surveillance, including under-recognition of at-risk patients, low surveillance utilization in clinical practice, and lower sensitivity of current tools for early-stage HCC detection. Treatment decisions are best made in a multidisciplinary fashion and are informed by several factors including tumor burden, liver dysfunction, performance status, and patient preferences. Although patients with NAFLD often have larger tumor burden and increased comorbidities compared to counterparts, they can achieve similar post-treatment survival with careful patient selection. Therefore, surgical therapies continue to provide a curative treatment option for patients diagnosed at an early stage. Although there has been debate about the efficacy of immune checkpoint inhibitors in patients with NAFLD, current data are insufficient to change treatment selection based on liver disease etiology

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Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137766/1/hep29248.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137766/2/hep29248_am.pd

Frequency and Outcomes of Abnormal Imaging in Patients With Cirrhosis Enrolled in a Hepatocellular Carcinoma Surveillance Program

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148235/1/lt25398_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148235/2/lt25398.pd

Survival and cost‐effectiveness of sorafenib therapy in advanced hepatocellular carcinoma: An analysis of the SEER–Medicare database

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135309/1/hep28881-sup-0001-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135309/2/hep28881_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135309/3/hep28881.pd

in-Utero Exposure to antibiotics and Risk of Colorectal Cancer in a Prospective Cohort of 18 000 adult offspring

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers\u27 medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. RESULTS: Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. CONCLUSION: Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood