Liver cell cancer surveillance practice in Nigeria: Pitfalls and future prospects.

Hepatocellular carcinoma (HCC) is a disease of public health concern in Nigeria, with chronic hepatitis B and C infections contributing most to the disease burden. Despite the increasing incidence of HCC, surveillance practices for early diagnosis and possible cure are not deeply rooted in the country. This article aims to review the current status of HCC surveillance in Nigeria, stressing the encounters, breaches, and potential prospects. Several factors, such as limited tools for screening and diagnostics, insufficient infrastructure, and low cognizance among the doctors, and the general public affect the surveillance practices for HCC in Nigeria. Moreover, the lack of standardized guidelines and protocols for HCC surveillance further intensifies the suboptimal diagnosis and treatment. Nevertheless, there are opportunities for refining surveillance practices in the country. This would be achieved through boosted public health sensitization campaigns, integrating HCC screening into routine clinical services, and leveraging technological developments for early detection and monitoring. Furthermore, collaboration between government agencies, healthcare providers, and international organizations can facilitate the development of comprehensive HCC surveillance programs personalized to the Nigerian setting. Thus, HCC surveillance practice faces substantial challenges. By addressing the drawbacks and leveraging prospects, Nigeria can improve HCC surveillance, with subsequent improved outcomes for individuals at risk of developing the disease.

Hepatocellular carcinoma surveillance: The road ahead.

Is the measurement of tumor marker levels effective for monitoring patients after the treatment of hepatocellular carcinoma? RECOMMENDATIONFor patients in whom tumor marker levels were elevated before treatment, tumor markers measured after treatment may serve as useful indices of the effects of treatment.(grade C1) 30

International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma

Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction.

Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics. After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification. In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance.

Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis

Hepatocellular carcinoma (HCC) is an important cause of death worldwide and an increasing problem in Western countries.1–3 In Australia and the USA an increase in the incidence of HCC over the past three decades has been documented.2,3 This has been attributed both to immigration from areas endemic for hepatitis B and to a cohort of individuals with chronic hepatitis C originally infected 20–40 years ago and now progressing through cirrhosis to HCC. The future is no brighter: the hepatitis C epidemic shows no signs of abating whereas non-alcoholic fatty liver disease (NAFLD) related to diabetes and obesity looms as a potential second wave of cirrhosis and HCC in developed countries.4 HCC generally arises in patients with cirrhosis on a background of chronic viral hepatitis, alcohol excess or other chronic liver diseases (NAFLD or haemochromatosis, for example). These diseases are opportunities for intervention and, through this, prevention of HCC both at an individual and at a population level. Effective hepatitis B vaccination programmes can prevent vertical and horizontal transmission leading to a reduction in HCC incidence. This has been documented in Taiwan where the incidence of childhood HCC declined following implementation of targeted (1984) and then universal (1986) neonatal vaccination.5 In Australia, universal neonatal hepatitis B vaccination is recommended with catch-up vaccination of preadolescents (10–13 years of age) not immunized at birth.6 Effective immunization against hepatitis C is not yet available, but screening of blood products has minimized transmission by this route and harm reduction strategies, such as needle exchange programmes, may help to decrease transmission among i.v. drug users. Likewise, strategies to reduce alcohol abuse and obesity in the community, if effective, would be expected to reduce the future incidence of HCC. Worldwide, hepatitis B is the most important cause of HCC and, in some regions, dietary aflatoxin exposure is a key cofactor. Public health measures to reduce aflatoxin exposure and chemopreventative agents to counteract the effects of this toxin are currently being evaluated.7 Treatment options for chronic viral hepatitis have improved dramatically over the past decade and provide an opportunity for intervention at a second stage in the pathogenesis of HCC. The combination of pegylated interferon and ribavirin achieves sustained response rates of approximately 50–55% in chronic hepatitis C. Sustained response in non-cirrhotic patients should prevent progression to cirrhosis and HCC provided other causes of liver injury, such as alcohol abuse and coinfection with hepatitis B, are also eliminated. Treatment of cirrhotic patients with hepatitis C may also reduce subsequent progression to HCC presumably by reducing ongoing hepatocellular injury, regeneration and repair and possibly through a direct antiproliferative effect of interferon.8–12 In chronic hepatitis B, treatment with nucleoside analogues is effective in suppressing viraemia, reducing inflammatory activity and slowing the progression of fibrosis. The nucleoside analogues lamivudine, adefovir and entecavir are now available for treatment of hepatitis B in Australia. Long-term treatment with entecavir appears to reduce the development of HCC in the infected woodchuck model of hepatocarcinogenesis.13 In humans, a prospective randomized controlled study of lamivudine in advanced hepatitis B fibrosis or established cirrhosis has shown a reduction in HCC occurrence from 7.4% in the control group to 3.9% in the treated group (P = 0.047).14 Probably, such benefits will be seen in treatment regimes using other agents.15 Likewise, prevention of cirrhosis by venesection in patients with haemochromatosis and, hopefully, future interventions in NAFLD will further reduce the incidence of HCC in other groups at risk.4,16 Although elimination of HCC through prevention and treatment of chronic liver disease should be the goal, the full impact of such strategies may be decades away. Early detection of HCC remains an important focus in the management of patients with advanced liver disease. Surveillance for HCC, generally by 6-monthly hepatic ultrasound and monitoring of α-fetoprotein, identifies smaller lesions that are more amenable to treatment and may result in a survival advantage though further evidence for the latter is required.17,18 Despite uncertainties regarding the benefits, HCC surveillance has been widely adopted by gastroenterologists. Offered the choice and provided with appropriate information, most cirrhotic patients will opt for surveillance.19 Protocols for the investigation and management of small lesions identified through surveillance have been developed.20 There is a range of treatment options depending on the size, number and location of tumours within the liver, the severity of the underlying liver disease and the age and general health of the patient. In patients with HCC confined to one lobe, adequate hepatic reserve and without significant portal hypertension, 5-year survival rates greater than 50% have been reported following hepatic resection.21 Recurrent HCC, reflecting both true recurrence and new primaries in a premalignant liver, is a major problem following resection. Adjuvant intra-arterial 131I lipiodol appears to reduce recurrence and improve survival when given following apparently curative resection for HCC.22 For those with advanced liver disease or significant portal hypertension, liver transplantation can offer prolonged survival provided the tumours are small in size and number and there is no extrahepatic or vascular spread.23 Donor shortages and the resulting waiting times remain key issues in transplantation for HCC. Finally, there have been major advances in local ablative therapies for HCC. Imaging-guided radiofrequency ablation, in particular, is emerging as an important method for the treatment of small lesions.24 For larger lesions, transarterial chemoembolization appears to offer a modest survival benefit.25 In the future, as our understanding of the molecular basis of hepatocarcinogenesis increases, new strategies for the management of HCC are likely to emerge.26,27 It is against this background that Gellert et al.28 report their 'real world' experience of HCC in this issue and emphasize the difficulties of delivering optimal care to those at greatest risk for this disease. The authors describe 151 patients with HCC managed at two large public hospitals in Sydney South West Area Health Service between 1993 and 2003. The median survival was only 5.1 months. Most of the patients (75%) presented with symptomatic disease. Only 18% were detected through surveillance. It is difficult to know whether surveillance was of benefit in this group because of small numbers and the confounding effect of lead-time bias. Nevertheless, surveillance patients were more likely to have small tumours potentially suitable for resection or transplantation. At a population level, surveillance for HCC is only likely to have an influence if the target population is identifiable, accessible and willing to participate. In this study, cirrhosis was previously undiagnosed in a significant number of cases meaning that surveillance would not have been considered. In addition, only 7% of those with chronic viral hepatitis had ever received antiviral therapy. We can only speculate as to whether family members of the 63 hepatitis B patients had previously been offered vaccination, but it is clear that opportunities to intervene in the natural history of chronic liver disease and HCC are being missed. Education of the medical community and the public regarding the established and potential benefits of vaccination, treatment of chronic liver disease and surveillance for HCC, should help. Patients with chronic liver disease can be relatively isolated by virtue of language difficulties or socioeconomic circumstances so that strategies need to be well targeted and appropriately supported. The proportion of Asian-born HCC patients rose from 38 to 53% from the first to the second 5-year period in the series reported by Gellert et al.28 The number of patients requiring interpreters increased from 44 to 65% over the same period. Addressing the increasing incidence of HCC in Australia will not be easy. We will need to set aside funds for education and plan for an increasing demand over a range of services including interpreters, hepatitis nurse specialists and clinicians. The demand for specialized HCC services in hepatology, radiology, surgery and transplantation has already increased significantly. At the time of writing, more than a quarter of adult patients awaiting liver transplantation in New South Wales have HCC and waiting times for therapeutic radiological interventions in HCC patients are beginning to cause concern. In developing nations, where HCC is most prevalent, the problems in equitably delivering the recent advances in the management of chronic liver disease and HCC are even greater. The real world poses real challenges in the prevention, detection and treatment of HCC.

Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper.

Introduction Hepatocellular carcinoma (HCC) mortality and incidence is increasing worldwide. Current guidelines recommend biannual surveillance with ultrasound (USS) and/or alpha-fetoprotein (AFP) to ensure early detection and prompt treatment, yet the benefit on patient outcomes is uncertain in the absence of high quality data. We aimed to describe the merits of HCC surveillance in a single-centre cohort with an ethnically diverse population. Methods We retrospectively identified patients diagnosed with HCC from 2010 to 2017. We determined whether HCC occurred on surveillance or not. We collected information including demographic data, aetiology and severity of liver disease, AFP levels, tumour size, initial treatment, survival status and cause of death. Results 101 cases were identified. Median age was 71 years (range 47–94), 75% were male. 63% were white and 25% from South Asian background. The commonest aetiology was Non-Alcoholic Fatty Liver Disease (NAFLD, 22.8%), followed by Alcohol-Related Liver Disease (ARLD, 19.8%), Hepatitis C (HCV, 21.8%) and Hepatitis B (HBV, 5%). 7/22 patients with HCV had achieved SVR. Only 1 received direct-acting antivirals (DAA) prior to HCC diagnosis. 25/101 patients were diagnosed on HCC surveillance; 11/101 presented with acute decompensated cirrhosis (9 were under a surveillance programme, 2 had failed to attend); 43/101 presented with symptoms and 22/101 were incidental findings. HCV was the predominant aetiology in those presenting symptomatically. AFP was normal in half of all cases. Of those on surveillance, 63% had AFP measured prior to diagnosis and 8.5% had a raised AFP when initial imaging was normal. 57% patients were Child’s A, 38% Child’s B and 5% Child’s C at diagnosis. Patients were more likely to have HCC diagnosed at an early stage on surveillance (68.6% vs 30.3%) and receive curative treatment (22.8% vs 12.1%) than the non-surveillance group. 1 and 3 year survival rates were greater on surveillance (67.7% vs 41.1% and 22.2% vs 8.16%, respectively). Median survival after diagnosis in the surveillance group was greater than those presenting for the first time. Conclusions Surveillance was associated with earlier stage cancers and receipt of potentially curative treatment. However, patients known to secondary care made up a minority of HCC diagnoses. Improving identification and diagnosis of cirrhosis in primary care may therefore help identify at-risk patients earlier, although not all patients will engage with follow-up. AFP measurement may identify additional cases of HCC that go undetected by USS, but should be weighed against potential patient harms from false-positive Results. Further studies should continue to inform an optimum HCC surveillance strategy.

Management of patients with hepatitis B virus-induced cirrhosis

Introduction: Hepatocellular carcinoma (HCC) surveillance detects early stage cancer, increases curative options and improves survival. Practice guidelines recommend HCC screening every 6 months in this population. Our previous study of adherence to HCC surveillance was not optimal. Our goal was to assess the improvement in adherence to HCC surveillance guidelines among patients with cirrhosis after implementation of QI measures. Methods: Previous study of adherence to HCC surveillance guidelines at Northwell Health Hepatology practice in 2016 (January 1st to December 31st) showed that routine surveillance every 6 months was 36%, and inconsistent surveillance was 60% (mean 10 ± 3 months). We retrospectively reviewed HCC surveillance among patients with cirrhosis after implementation of dedicated patient education and monthly reminder to health care providers. Patients with cirrhosis having visits between January 1st 2017 and March 1st 2018 were included in this follow-up study. Records were reviewed for demographics, liver disease, surveillance modality, interval and results. Prior HCC was excluded. Results: A total of 933 patients were included. Demographics and surveillance modalities are listed in table 1 and 2 respectively. Eighty six percent had routine surveillance every 6 months; 14% had inconsistent surveillance (range 8 to 12 months, mean 10 ± 2 months). Mean surveillance interval was 6 ± 2 months. Thirty six de novo HCC (3.9%) were detected, the majority had alcohol associated liver disease (56%). Eighty nine percent were single tumors (n=32), 11% multifocal (n=4), none were metastatic. All met Milan criteria for liver transplantation (OLT). Twenty (56%) were referred to OLT, 12 (33%) underwent resection and 4 (11%) radiofrequency ablation. Conclusion: Our study illustrates that implementation of QI measures improve HCC surveillance. In our population, 3.9% of patients with cirrhosis were detected with de novo HCC by routine surveillance. The majority were single tumors, early cancers and eligible for curative therapy, including resection and OLT. There was a marked improvement in adherence to standard HCC surveillance from previous study in 2016 of 36% to 86% following implementation of our QI measures. Our study shows that QI measures by patient education and physician reminders increase adherence to practice guidelines significantly and improve quality of patient care.922_A Figure 1. Patient Demographics and Characteristics.922_B Figure 2. Hepatocellular Carcinoma (HCC) Surveillance Modality.

Hepatitis C and Hepatocellular Carcinoma: Grist for the Mill

Hepatocellular carcinoma (HCC) is the seventh most common malignancy worldwide. HCC meets all the criteria established by the World Health Organization for performing surveillance on those at-risk for developing cancer. Although there are consensus guidelines in the United States, Europe, and Asia for HCC surveillance, it is unclear if these guidelines are regularly implemented in routine practice to optimize real-life clinical outcomes. We reviewed the current literature on the adherence to current HCC practice guidelines by the American Association for the Study of Liver Diseases (2009), the European Association for the Study of the Liver (2012), and the Asia Pacific Association for the Study of the Liver (2010) for screening/surveillance and outcomes of optimal versus poor adherence. We performed PubMed search for relevant articles regarding HCC surveillance and screening worldwide. Currently, HCC screening is underutilized to a large extent. In most studies, the adherence to HCC screening and surveillance is suboptimal. Various patient, provider, and health care system factors may have all contributed to such nonadherence. Strategies to improve HCC screening and surveillance are urgently needed for early HCC detection and improved survival of HCC patients. Further research is needed to elucidate the various medical and/or cultural knowledge, belief, and practice patterns that can lead to barriers to HCC screening and surveillance at both patient and provider levels. These data will help focus and target advocacy and educational efforts to improve HCC surveillance at all levels: patients, providers, and health care system/government.

Hepatocellular carcinoma diagnosis and surveillance: Socioeconomic factors don’t seem to matter, unless you are an immigrant