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

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

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

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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

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Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138269/1/hep29286.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138269/2/hep29286_am.pd

Patient and provider‐level barriers to hepatitis C screening and linkage to care: A mixed‐methods evaluation

Achieving practice change can be challenging when guidelines shift from a selective risk‐based strategy to a broader population health strategy, as occurred for hepatitis C (HCV) screening (2012‐2013). We aimed to evaluate patient and provider barriers that contributed to suboptimal HCV screening and linkage‐to‐care rates after implementation of an intervention to improve HCV screening and linkage‐to‐care processes in a large, public integrated healthcare system following the guidelines change. As part of a mixed‐methods study, we collected data through patient surveys (n = 159), focus groups (n = 9) and structured observation of providers and staff (n = 9). We used these findings to then inform domains for the second phase, which consisted of semi‐structured interviews with patients across the screening‐treatment continuum (n = 24) and providers and staff at primary care and hepatology clinics (n = 21). We transcribed and thematically analysed interviews using an integrated inductive and deductive framework. We identified lack of clarity about treatment cost, treatment complications and likelihood of cure as ongoing patient‐level barriers to screening and linkage to care. Provider‐level barriers included scepticism about establishing HCV screening as a quality metric given competing clinical priorities, particularly for patients with multiple comorbidities. However, most felt positively about adding HCV as a quality metric to enhance HCV screening and linkage to care. Provider engagement yielded suggestions for process improvements that resulted in increased stakeholder buy‐in and real‐time enhancements to the HCV screening process intervention. Systematic data collection at baseline and during practice change implementation may facilitate adoption and adaptation to improve HCV screening guideline implementation. Findings identified several key opportunities and lessons to enhance the impact of practice change interventions to improve HCV screening and treatment delivery.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155892/1/jvh13278.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155892/2/jvh13278_am.pd

The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre

Aliment Pharmacol Ther   31 , 625–633The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined.To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients.Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed.In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months–25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01–1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17–3.08) and stage of disease (HR 1.51, 95%CI 1.16–1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26–0.88). There were no significant differences regarding clinical presentation, disease stage ( P  = 0.98), and survival ( P  = 0.51) between intra- and extrahepatic cholangiocarcinoma.Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79101/1/j.1365-2036.2009.04218.x.pd