2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Frequent expression of PD-L1 in lymphocyte-rich hepatocellular carcinoma: A report of 4 cases.

BACKGROUND: Programmed death ligand 1 (PD-L1) is an immune checkpoint inhibitor. PD-L1 binds to its receptor programmed death receptor (PD-1) expressed by immune cells and plays a key role in regulating immune responses. Engagement of PD-L1 on cancer cells and PD-1 on immune cells avoid destruction of tumour cells by immune cells. Immunostaining with PD-L1 has been suggested as a biomarker predictive of antiPD-L1 immunotherapy. Lymphocyte-rich hepatocellular carcinoma (LrHCC) is a rare histological HCC subtype which is characterised by neoplastic epithelial cells intermixed with numerous immune cells. METHODS: Here in we investigated immunohistochemical PD-L1 expression in 4 cases of LrHCC. Tumour proportion score (TPS) and immune cell score was recorded. Immunophenotypic characterization of the tumour and inflammatory cells was also done. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) assay as performed in all four tumours. RESULTS: Expression of PD-L1 was demonstrated in tumour epithelial cells and immune cells in all four cases. Incomplete to membranous staining was demonstrated in the tumour cells. Tumour proportion score (TPS) was 1.2-20 %. Immune cells demonstrated membranous and cytoplasmic immunostaining. Immune cell score was ≥1 % to >10 %. CONCLUSION: PD-L1 expression in both tumour and immune cells suggests distinct immunogenic feature and potential role of antiPD-L1 therapies in cases with inoperable disease.

Post-COVID-19 cholangiopathy: Current understanding and management options.

Post-coronavirus disease 2019 (COVID-19) cholangiopathy (PCC) is a rare but life-threatening complication of COVID-19 infection. PCC typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver disease. The pathogenesis of PCC is little understood. Hepatic injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for cholangiocytes. Though PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients, it is considered as a separate and unique entity in the literature. Various treatment options like ursodeoxycholic acid, steroids, plasmapheresis, and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited success. We have noticed significant improvement in liver function with antiplatelet therapy in a couple of patients. PCC can progress to end-stage liver disease necessitating liver transplantation. In this article, we discuss the current knowledge of PCC focusing on its pathophysiology, clinical manifestations, and management strategies.

Liver Cirrhosis and Portal Hypertension: How to Deal with Esophageal Varices?

The understanding of pathogenesis of portal hypertension in patients with liver cirrhosis continues to evolve. In addition to progressive fibrosis, cirrhosis is characterized by parenchymal extinction and vascular remodelling, causing architectural distortion. Existence of prothrombotic state and more recently, intestinal bacterial dysbiosis are recently described in the pathogenesis of portal hypertension. Clinically significant portal hypertension (CSPH) is an important prognostic milestone in patients with liver cirrhosis. This is a pre-symptomatic phase that predicts the development of varices, ascites and importantly increased risk of Hepatocellular carcinoma (HCC). CSPH is associated with significantly reduced survival. Endoscopic surveillance is necessary in these patients. Non-selective Beta-blocker is the preferred therapy for primary prophylaxis in the management of portal hypertension. Patients with acute variceal bleed should be resuscitated appropriately, followed by vasoactive drugs and endoscopic therapy. Early TIPS should be considered in those with refractory bleed or in endoscopic treatment failure. Application of artificial intelligence and machine learning may be useful in future for identifying patients at risk of variceal hemorrhage.

Biphenotypic Immunohistochemical Features and NTRK1 Amplification in Intermediate Cell Carcinoma of the Liver.

Intermediate cell carcinoma is one of the rarest forms of primary liver cancer comprising relatively monomorphic populations of neoplastic epithelial cells demonstrating simultaneous positivity of both hepatocyte and cholangiocyte immunohistochemical markers. Here in, we describe an adult male patient who underwent left hepatectomy for a large liver tumor. The pathological and immunohistochemical analysis revealed the malignant primary liver cancer with intermediate cell morphology and mixed immunophenotypic features consistent with intermediate cell carcinoma. Furthermore, the genomic profiling using the Next-generation sequencing (NGS) platform demonstrated that there is a novel amplification with copy number gain 12 (12 gene copies) in the Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1) gene, being an oncogenic driver of intermediate cell carcinoma. This is the first case report with the amplification in NTRK1 and emphasizes the importance of molecular oncology.

Nonalcoholic Steatohepatitis: A Rapidly Increasing Indication for Liver Transplantation in India.

Background and aims: Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. Methods: The study population was stratified into Period 1 (2009-2014) and Period 2 (2015-2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. Results: Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19-3.22). Conclusion: NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.

Versatility of Anabolic Androgenic Steroid-Induced Hepatotoxicity.

The modified derivatives of testosterone, termed as androgenic steroids are indicated in the management of hypogonadism, visceral obesity and metabolic disorders. Anabolic androgenic steroids (AASs) however are surreptitiously used by athletes and body builders for cosmetic purpose owing to their anabolic effects on muscle mass and strength. The unsurveilled use of AASs subjects these users to various side effects involving multiple systems such as the endocrine, genitourinary, hepatobiliary, central nervous, musculoskeletal and psychosocial system. The liver is a hormone-sensitive organ owing to abundance of androgen receptors and is vulnerable to a wide array of hepatotoxicity ranging from asymptomatic liver enzyme elevation to life-threatening subacute liver failure. The type of drug-induced liver injury (DILI) due to AASs can be hepatocellular injury, cholestasis, fatty liver disease, chronic vascular injury and neoplastic disease. Herein, we report three cases of AAS-related DILI associated with AAS abuse.

Hereditary Persistence of Alpha-Fetoprotein in Chronic Liver Disease-Confusing Genes!

Alpha-fetoprotein (AFP) is a glycoprotein secreted by the embryonic liver and is expressed in tumours with high mitotic index such as hepatocellular carcinoma (HCC) and germ cell tumours. Detection of elevated AFP is strongly associated with underlying HCC or occasionally germ cell tumour. Modest elevation of AFP can be observed in patients with chronic viral hepatitis particularly with active replication. Very rarely, incidental detection of raised AFP in a genetically susceptible individuals has been reported in the absence of the underlying malignant process. This condition is termed as hereditary persistence of AFP (HPAFP), a rare disorder with an autosomal dominant pattern of inheritance. HPAFP should be suspected in patients with high AFP in the absence of radiological evidence of HCC or germ cell tumour. The diagnosis is confirmed by the identification of AFP gene mutation. AFP gene is located in the long arm of chromosome 4. The most common single-nucleotide polymorphism in HPAFP is 119 G > A, rs587776861, interestingly reported only in six family clusters worldwide. Despite being described as a benign disorder, its implication in patients with underlying chronic liver disease needs further clarification. Here, we describe 3 patients in their forties with chronic liver disease and persistently elevated levels of AFP, where genetic studies confirmed HPAFP. None of our patients had HCC despite extensive investigations.

Propensity Score-Matched Analysis of Posttransplant Outcomes in Living Donor Liver Transplantation for Older Adult Recipients.

The impact of increasing recipient age on morbidity and mortality following living donor liver transplantation (LDLT) remains controversial. The study aims to analyze the impact of recipient age on outcomes following LDLT. Data on adult LDLTs performed between November 2009 and February 2020 were retrieved from a prospectively maintained database. Patients were stratified into 2 groups based on recipient age: 18 to 65 years (younger adults) and >65 years (older adults). Propensity score matching (PSM) using nearest-neighbor matching was used to match each older recipient with up to 2 younger adult recipients using multiple preoperative parameters. Outcomes evaluated were duration of ventilation, need for reintubation, tracheostomy, intensive care unit (ICU) readmission, length of ICU and hospital stays, postoperative complications, reoperation within 90 days, and patient survival. A total of 801 adult LDLT recipients were included in the study; 751 (93.7%) were younger adults, and 50 (6.3%) were older adults. Older recipients were more likely to be diabetic (60.0% versus 39.7%) and hypertensive (44.0% versus 20.4%) with preexisting cardiac disease (28.0% versus 11.2%). However, their pretransplant Model for End-Stage Liver Disease score was significantly lower (14.5 versus 17.7), and they were more likely to receive a transplant because of hepatocellular carcinoma (38.0% versus 17.7%). Older recipients had longer durations of ventilation after LT both before (3.7 versus 1.9 days) and after PSM (4.0 versus 1.5 days). After PSM, the 30-day (13.0% versus 2.4%), 90-day (15.2% and 2.4%), and overall mortality rates (21.7% versus 7.1%) were significantly higher for older recipients when compared with younger recipients. There was no difference between the younger and older recipients with respect to other postoperative outcomes. This propensity score-matched study shows that the older LDLT recipients have higher 30-day, 90-day, 1-year, and 5-year mortality rates when compared with matched younger counterparts.

Patient blood management in a patient with multiple red cell antibodies (anti-C, anti-e, and anti-K) undergoing liver transplant in South India: A team approach.

End-stage liver disease (ESLD) patients undergoing liver transplant (LT) surgery are often multiply alloimmunized and pose significant challenges to the transfusion services in terms of red cell cross-match incompatibility, unpredictable blood requirements, and often lead to significant delays in availing compatible red cell units. We report a case of a 64-year-old female from Bahrain, a known case of hepatitis C-related ESLD referred for LT surgery. She had a history of multiple uneventful transfusions in the preceding year. Her blood group was A-positive, direct antiglobulin test, and cold antibodies were negative. Indirect antiglobulin test was positive, and antibody identification confirmed the presence of anti-C, anti-e, and anti-K. Her red cell phenotype was R2R2 and Kell negative (C-c+E+e-K-). The patient was started on erythropoietin. Requests for R2R2 and Kell negative units were sent to various blood banks across the country. After >800 A/O group units phenotyping and a waiting period of 6 weeks, two compatible R2R2 phenotypes and Kell negative could be arranged in-house and three units were received from Gurgaon, North India. Intraoperative management included blood preservation techniques including cell salvage, antifibrinolytic drug, and monitoring using thromboelastography. The estimated blood loss was 350 ml with pre- and postoperative Hb 10.4 gm% and 9.2 gm%, respectively. She received intraoperatively two units of single-donor platelet and four units of fresh frozen plasma and postoperatively one unit of leukocyte-depleted-packed red cells and doing well at 12-month follow-up. This case highlights the importance of advance immunohematology for timely detection of alloimmunization and providing antigen-negative compatible units, proper communication between the transfusion specialists, and the clinical team for proper patient blood management as well as the need for central rare donor registry program to avoid delays in providing compatible blood in such inevitable cases.

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.

Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

Hepatitis B immunoglobulin prophylaxis after liver transplantation: experience in a tertiary transplant centre.

BACKGROUND: Prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs can prevent hepatitis B virus (HBV) recurrence after liver transplant (LT). AIM: To determine the efficacy and cost of maintaining immunoprophylaxis with HBIG and hyperimmune plasma (HIP) for 6 months after LT. MATERIAL & METHODS: The study included 22 HBV related LT recipients who were on entecavir and either HBIG or HIP for 6 months. Post transplant HBIG or HIP dose and cost incurred towards prophylaxis were noted. The cost of 200 IU of HBIG at the time of study was Rs 8250/- (US Dollars 135) and that of 2000 IU of HIP was Rs 8000/- (USD 130.7). The loading and maintenance costs at end of 6 months were compared between the two groups. Response to HBIG and HIP was assessed by checking for HBsAg reactivity, anti HBs titer response and HBV DNA viral load. STATISTICAL ANALYSIS: Median and range, Kruskal Wallis (KW) sign rank Sum Test and Correlation Coefficient (r2) was used for analysis. RESULTS: Thirteen recipients received HBIG and 9 recipients HIP. The anti HBs response to HIP was significantly high compared to HBIG (KW Sign rank Sum test P < 0.05); titers remained high until the study period. Between 8 and 30 days, the titer achieved by both HBIG and HIP was similar (KW Sign rank Sum test not significant). Despite low anti HBs titer of <100 IU/L, none of the recipients on HBIG had HBsAg reactivity while 3 on HIP had transient HBsAg positivity. The total cost with HBIG was 13.9 times the cost of HIP. CONCLUSION: HIP immunoprophylaxis in combination with entecavir achieves a high anti HBs titer at a significant low cost during anhepatic and loading phase. HBV reactivation rates with HBIG and HIP is low despite low anti HBs titer.

Macrophage secretory products induce an inflammatory phenotype in hepatocytes.

AIM: To investigate the influence of macrophages on hepatocyte phenotype and function. METHODS: Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophage-conditioned medium on HepG2 mRNA and protein expression determined. The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus (HCV) infection. RESULTS: Conditioned media from macrophages, but not monocytes, induced a transient morphological change in hepatocytes associated with upregulation of vimentin (7.8 ± 2.5-fold, P = 0.045) and transforming growth factor (TGF)-ß1 (2.6 ± 0.2-fold, P < 0.001) and downregulation of epithelial cadherin (1.7 ± 0.02-fold, P = 0.017) mRNA expression. Microarray analysis revealed significant upregulation of lipocalin-2 (17-fold, P < 0.001) and pathways associated with inflammation, and substantial downregulation of pathways related to hepatocyte function. In patients with chronic HCV, real-time polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA (F0 1.0 ± 0.3, F1 2.2 ± 0.2, F2 3.0 ± 9.3, F3/4 4.0 ± 0.8, P = 0.003) and protein expression (F1 1.0 ± 0.5, F2 1.3 ± 0.4, F3/4 3.6 ± 0.4, P = 0.014) with increasing liver injury. High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase (MMP)-9 in macrophage-conditioned medium, and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-ß1 (2.9 ± 0.2 vs 1.04 ± 0.1, P < 0.001) in macrophage-conditioned media treated HepG2 cells. In patients with chronic HCV infection, hepatic mRNA expression of CD163 (F0 1.0 ± 0.2, F1/2 2.8 ± 0.3, F3/4 5.3 ± 1.0, P = 0.001) and MMP-9 (F0 1.0 ± 0.4, F1/2 2.8 ± 0.3, F3/4 4.1 ± 0.8, P = 0.011) was significantly associated with increasing stage of fibrosis. CONCLUSION: Secreted macrophage products alter the phenotype and function of hepatocytes, with increased expression of inflammatory mediators, suggesting that hepatocytes actively participate in liver injury.

Non-invasive assessment of fibrosis in liver grafts due to hepatitis C virus recurrence.

Hepatitis C virus (HCV) infection has become the most common indication for liver transplantation in the United States and Europe. Recurrence of HCV is universal in all liver graft recipients, but the natural history of the disease is variable with some patients displaying slowly progressive liver injury, while approximately 30% become cirrhotic within five yr of surgery. Currently, liver biopsy is the reference standard to assess liver injury in the post-transplant setting. But biopsy is associated with complications such as bleeding and pain, as well as the risk of sampling error and discordance in reporting between histopathologists. Thus, as in the pre-transplant setting, there is increasing attention being drawn to the use of non-invasive tests of liver fibrosis. This review examines the role of non-invasive assessment of hepatic fibrosis in the post-transplant setting including simple tests such as aspartate aminotransferase-to-platelet ratio index, the Benlloch formula, London Transplant Centre score, and finally transient elastography. The authors assess the respective advantages and disadvantages of the tests and consider how non-invasive tests of liver fibrosis can be utilized in the future management of post-transplant HCV infection.

Treatment of autoimmune hepatitis: a review of current and evolving therapies.

Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune, and histological parameters, and exclusion of other liver diseases. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second-line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab, ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.

Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered.

BACKGROUND/AIMS: Currently the diagnosis and severity of hepatic steatosis can be established accurately only by liver biopsy. Previous small studies found that steatosis measured by magnetic resonance spectroscopy (MRS) and imaging (MRI) correlated with histological assessment of liver triglyceride content. However, the accuracy of MRS/MRI for grading the severity of steatosis has not been addressed. The aims of this study were (1) to determine whether MRS and MRI can discriminate grades of steatosis in a large cohort of consecutive patients with a wide spectrum of liver disease aetiology and severity (2) to evaluate the effect of hepatic fibrosis, inflammation and iron on quantitation of intrahepatocellular lipid (IHCL) by these techniques. METHODS: Ninety-four sequential patients who underwent percutaneous liver biopsy or liver resection had MRS and MRI (Dixon in phase/out of phase (Dixon IP/OP) and with/without fat saturation (+/-FS) images) to determine IHCL. Histology was used as the reference standard. RESULTS: Close relationships were observed between the percentage of steatosis estimated by histology and MRS/MRI (r(s)=0.88 p<0.001 for all techniques). However, separate equations were required for the percentage of steatosis to avoid underestimation by imaging for patients with moderate or advanced fibrosis. All techniques had good diagnostic accuracy for mild steatosis (AUROC > or =0.87) as well as moderate/severe steatosis (AUROC > or =0.89). Hepatic inflammation and mild iron deposition (Perls' grade 1 and 2) did not interfere with estimation of steatosis by imaging. CONCLUSIONS: MRS and MRI had good accuracy for grading the severity of steatosis in subjects with liver disease, provided that stage of fibrosis was considered.

The effect of ethnicity on the presentation and management of oesophageal and gastric cancers: a UK perspective.

BACKGROUND: Studies show disparities in the management of oesophageal and gastric cancers between different ethnic groups. Asian patients with gastric adenocarcinoma present with less advanced disease and are more likely to undergo curative resection. For oesophageal cancer, the rate of surgery in Black patients is half that of Caucasians. However, these studies originate from the United States where demographics differ from that of the UK. METHODS: We undertook a 5-year retrospective audit of patients diagnosed with oesophageal and gastric cancers at City Hospital, Birmingham (UK), which serves three major ethnic groups: Caucasians, Blacks and Asians. RESULTS: Data were extracted from 244 patients' records that included 133 gastric and 111 oesophageal cancers. Caucasians were more likely to present within 3 months of symptom onset than Asians or Blacks. Asians were less likely to be referred for urgent endoscopy than Caucasians or Blacks (P<0.05). Significant differences in reported symptoms were found between ethnic groups with Caucasians more likely to report dysphagia and less likely to describe abdominal pain than other ethnic groups. There was a lower rate of curative operation for Asians but this did not reach significance. CONCLUSION: Ethnicity seems to influence health-seeking behaviour, with Caucasians more likely to present earlier for medical attention and Asian patients less likely to be referred for urgent endoscopy. Improvements in symptom education amongst patients and health professionals alike may accelerate referral and improve outcome. The favourable disease patterns reported in the United States 'Asians' and the lower surgery rates reported in the United States 'Blacks' are not shown in this UK population.