qFIBS: An Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) imaging-based tool to provide an automated quantitative assessment of histological features pertinent to NASH. APPROACH AND RESULTS: Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve values (qFibrosis [0.870-0.951; 95% confidence interval {CI}, 0.787-1.000; P < 0.001], qInflammation [0.820-0.838; 95% CI, 0.726-0.933; P < 0.001), qBallooning [0.813-0.844; 95% CI, 0.708-0.957; P < 0.001], and qSteatosis [0.939-0.986; 95% CI, 0.867-1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades. CONCLUSIONS: qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.

Validation of the Expanded Baveno-VI Criteria for Screening Gastroscopy in Asian Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria. AIM: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection. METHODS: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV). RESULTS: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively. CONCLUSION: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.

Comparison of Hepatocellular Carcinoma in Patients with Cryptogenic Versus Hepatitis B Etiology: A Study of 1079 Cases Over 3 Decades.

BACKGROUND: Traditionally in Asia, hepatitis B (HBV) accounts for the majority of hepatocellular carcinoma (HCC), but increasingly, non-viral or nonalcoholic steatohepatitis (NASH) etiology may play a more prominent role with current socioeconomic changes. There remains a paucity in data comparing NASH-HCC to HBV-related HCC. In this study, we explored the differences in clinical characteristics between HBV- and cryptogenic-related HCC. METHODS: Patients with HCC seen in the Department of Gastroenterology and Hepatology, Singapore General Hospital were enrolled in an ongoing database since 1980. Patients with HCC attributed to HBV or cryptogenic etiology were identified. Comparison of clinical characteristics was performed between the two groups. RESULTS: There were 916 HBV-HCC patients and 163 cryptogenic HCC patients, accounting for 70.9% and 12.6% of the total HCC cases (1292 patients), respectively. Out of the total cohort enrolled from 1980 to 2005, the ratio of cryptogenic to HBV patients was 1:6.7, while from 2006 to the current year, the ratio of cryptogenic to HBV patients has increased significantly to 1:3.9. Relative to patients with HBV, cryptogenic HCC patients were older (67.6 vs. 59.4 years old; p < 0.001), had lower proportion of male patients (69.9% vs. 83.8%; p < 0.001), and had higher incidence of smoking (32.2% vs. 25.8%; p = 0.008). HBV group had higher alanine transaminase (60.9 ± 85.7 U/L vs. 48.0 ± 52.1 U/L; p = 0.003), hemoglobin (12.7 ± 2.28 g/dL vs. 12.0 ± 2.46 g/dL, p < 0.001), albumin (32.9 ± 6.8 g/L vs. 31.3 ± 7.7 g/L; p = 0.007), and prothrombin time (13.2 ± 2.95 s vs. 12.7 ± 2.01 s, p = 0.023), as compared to the cryptogenic group. Cryptogenic HCC patients presented more frequently with unifocal HCC (55.2% vs. 46.5%; p = 0.002). There was no difference in the proportions of patients receiving surgical resection in both groups (23.5% in HBV group vs. 17.9% in cryptogenic group; p = 0.202). Cox regression analysis revealed no survival difference between cryptogenic-related HCC and HBV-related HCC (p = 0.367). CONCLUSION: Temporal trends suggest that HCC attributed to HBV is on the decline, while cryptogenic- or NASH-related HCC is an emerging clinical entity. A paradigm shift in approach to screening, surveillance, and management of HCC may be required in view of the changing landscape of HCC epidemiology into an increasing non-viral etiology.

Probability-based interpretation of liver stiffness measurement in untreated chronic hepatitis B patients.

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography is a popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize patients and do not clearly indicate the confidence of diagnosis. AIM: We derived and validated probability functions of fibrosis and cirrhosis based on LSM and determined the effect of alanine aminotransferase (ALT) on the scores. METHODS: Consecutive chronic hepatitis B patients who underwent liver function tests, LSM, and liver biopsies at six European and Asian centers (2/3 in the training cohort and 1/3 in the validation cohort) were recruited. Binary logistic regression was performed to predict the probabilities of different fibrosis stages based on LSM and/or ALT. RESULTS: A total of 1,051 patients were included in the final analysis (53 % with ALT ≥ 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The probability functions (LiFA-HBV score) with and without ALT adjustment closely mirrored the proportion with different fibrosis stages in both the training and validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear relationship with LSM for each fibrosis stage (r (2) = 0.018-0.13). Based on relative integrated discrimination improvement, the addition of ALT to the LiFA-HBV score increased the correct reclassification of F3-4 and F4 by 5 and 17 %, respectively. CONCLUSIONS: ALT increases LSM in a linear fashion in chronic hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately predicts the probability of fibrosis. ALT adjustment increases the rate of reclassification modestly and is not essential.

Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis.

BACKGROUND: The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting. METHODS: In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 109 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 109 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 109 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164. FINDINGS: Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I2<25%) for most estimates. INTERPRETATION: Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective ß-blocker treatment. FUNDING: None.

Hepatic venous-portal gradient (HVPG) measurement: pearls and pitfalls.

Hepatic venous pressure gradient (HVPG) is the gold-standard for measurement of portal hypertension, a common cause for life-threatening conditions such as variceal bleeding and hepatic encephalopathy. HVPG also plays a crucial role in risk stratification, treatment selection and assessment of treatment response. Thus recognition of common pitfalls and unusual hepatic venous conditions is crucial. This article aims to provide a radiographical and clinical guide to HVPG with representative clinical cases.

Comparisons between non-alcoholic steatohepatitis and alcohol-related hepatocellular carcinoma.

BACKGROUND/AIMS: Non-alcoholic liver disease and alcoholic liver disease begin as simple steatosis that may progress to steatohepatitis and ensuing liver-related complications such as cirrhosis and hepatocellular carcinoma (HCC). We explored differences in characteristics between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis-related (ASH) HCC. METHODS: NASH and ASH patients were identified from our department's prospective HCC database. A total of 54 and 45 patients met predefined inclusion and exclusion criteria for the NASH-HCC and ASH-HCC groups, respectively. Clinical, biochemical and tumor characteristics were studied. RESULTS: NASH-HCC patients were older compared to ASH-HCC patients (72±9 vs. 66±9 years, P<0.001) and less male predominant (65% vs. 98%, P<0.001). Prevalence of diabetes mellitus (78% vs. 36%, P<0.001) and hypertension (80% vs. 58%, P<0.001) were significantly higher in the NASH-HCC group. Liver function tests and Child-Pugh scores were similar. There were no differences in alpha-fetoprotein level, lesions found at diagnosis (unifocal/multifocal) or prevalence of portal vein invasion. In both groups, almost half of the patients were in TNM stage 4 at the time of diagnosis and more than 50% of patients were not suitable for any therapy. Median survival in the NASH-HCC and ASH-HCC groups were 13 and 7 months respectively (P=0.113). CONCLUSION: Despite significant differences in demography of the NASH-HCC and ASH-HCC groups, liver and tumor characteristics were comparable. Most patients were diagnosed late and were not amenable to curative or locoregional therapies. Better characterization of patients with NASH and ASH at risk of HCC is necessary to optimize screening, surveillance, and management strategies.

Clinical validation of the chronic liver disease questionnaire for the Chinese population in Singapore.

BACKGROUND AND AIM: Assessment of health-related quality-of-life (HRQOL) in patients with chronic liver disease (CLD) requires the use of validated instruments that are understood by patients in their native language. We previously translated the Chronic Liver Disease Questionnaire into the Singapore-Mandarin version (CLDQ-SG). This study aims to examine the internal consistency and validity of the CLDQ-SG in patients with CLD. METHODS: We conducted a cross-sectional study of adult patients with CLD seen in a tertiary center in Singapore who completed both the CLDQ-SG and Short Form Health Survey 36 version 2 (SF-36v2) questionnaires. Internal consistency of the CLDQ-SG was assessed using Cronbach's alpha coefficient. Convergent and divergent validity of the SF-36v2 was assessed using the Spearman correlation coefficient, while discriminant validity was assessed using the Jonckheere-Terpstra test for trend. Exploratory factor analysis was performed to evaluate the factor structure of the CLDQ-SG. RESULTS: We enrolled 242 subjects (68.2% males, median age 67 years). Predominant etiology of CLD was chronic hepatitis B. Severity of CLD was divided into noncirrhotic (67.3%), compensated cirrhosis (24.0%), and decompensated cirrhosis (8.7%). Item convergent and discriminant validity of the CLDQ-SG was excellent, with 100% scaling success in all six domains. All domains exhibited good internal consistency, with Cronbach's α > 0.70. We observed a consistent trend of a reduction in mean CLDQ-SG score in the three groups reflecting the discriminant validity of the CLDQ-SG to assess changes in HRQOL in different severities of CLD. Factor analysis of the CLDQ-SG demonstrated an independent factor assessing sleep. CONCLUSION: The Singapore-Mandarin version of CLDQ-SG is a valid and reliable instrument to measure HRQOL in patients with CLD.

Rapid and Safe Crossing of the Chasm: Application of a Flipped Learning Framework for the Clipping Over the Scope Technique.

Training practicing physicians to adopt new technology may be difficult because most endoscopy training is given during fellowship training. As such, the adoption of new technology in gastroenterology is typically slow. We designed our course to train our cohort of practicing physicians using flipped learning, a pedagogical approach in which instructional cognitive content is delivered to the individual instead of the group, usually through online platforms and outside of the classroom. We describe our methods and results of the training courses on the techniques of clipping over the scope for gastrointestinal bleeding and endoscopic balloon dilation.

Clinical spectrum of non-alcoholic fatty liver disease in patients with diabetes mellitus.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully. AIM: We explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients. METHODS: This is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software. RESULTS: Among 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness. CONCLUSIONS: Our study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.

Idiopathic portal hypertension in patients with HIV infection treated with highly active antiretroviral therapy.

OBJECTIVES: Idiopathic portal hypertension (IPH) is the presence of PH in the absence of liver disease. Recently, IPH was reported in HIV patients on highly active antiretroviral therapy (HAART). We describe for the first time the hepatic and systemic hemodynamic profile, liver stiffness, and histological features of eight patients with HIV-related IPH. METHODS: HIV-positive patients were identified from our IPH database over 3 years. RESULTS: Five patients presented with variceal bleeding, two with splenomegaly, and one with ascites. All had large esophageal varices. Median hepatic venous pressure gradient (HVPG) was 8 mm Hg (range 3.5-14.5), clearly underestimating the true portal pressure. This is probably because of a presinusoidal component of PH and because of the presence of intrahepatic venous collaterals. Median liver stiffness was 8.9 kPa (range 6.8-14.9) and was unreliable in predicting the presence of fibrosis or of esophageal varices. The main histological features were absence of portal vein radicles and areas of regenerating hepatocytes. Six patients (75%) developed portal vein thrombosis during a 2-year follow-up. CONCLUSIONS: There is a subset of HIV patients without cirrhosis but with PH compatible with IPH. In these patients, the hepatic and systemic hemodynamic profile is similar to other forms of IPH. The histological profile reflects an underlying vascular disorder affecting the medium-sized portal vein branches. Development of portal vein thrombosis is a frequent complication and requires close monitoring.

Optimal liver stiffness measurement values for the diagnosis of significant fibrosis and cirrhosis in chronic liver disease in Singapore.

INTRODUCTION: Despite the widespread use of transient elastography for non-invasive assessment of liver fibrosis, the optimal cut-off liver stiffness measurement (LSM) values remain unclear. This study aimed to validate the optimal cut-off LSM values for significant fibrosis and cirrhosis in patients with chronic liver disease (CLD). METHODS: Prospective multicentre data of CLD patients who underwent paired liver biopsy and LSM was analysed to determine the optimal cut-off LSM values for predicting significant fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4). A high-quality cohort was selected by excluding those with failed LSM and invalid LSM readings. RESULTS: Of the 481 patients recruited, 322 fulfilled the pre-defined quality criteria. CLD aetiology was chronic hepatitis B (CHB) in 49%, non-alcoholic steatohepatitis (NASH) in 16% and chronic hepatitis C (CHC) in 12%. Area under the receiver operating characteristic curve for LSM was 0.775 (95% confidence interval [CI] 0.724-0.826) for significant fibrosis and 0.810 (95% CI 0.738-0.882) for cirrhosis. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 13 kPa for cirrhosis in the general cohort. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 12 kPa for cirrhosis for both CHB and CHC, while the corresponding values for NASH were 11 kPa and 15 kPa. CONCLUSION: Optimal cut-off LSM values should be selected based on disease aetiology. In Singapore, the optimal cut-off LSM values for CHB and CHC are 9 kPa for significant fibrosis and 12 kPa for cirrhosis. Optimal cut-off values for NASH require further validation.

Quantification of hepatic steatosis in chronic liver disease using novel automated method of second harmonic generation and two-photon excited fluorescence.

The presence of hepatic steatosis (HS) is an important histological feature in a variety of liver disease. It is critical to assess HS accurately, particularly where it plays an integral part in defining the disease. Conventional methods of quantifying HS remain semi-quantitative, with potential limitations in precision, accuracy and subjectivity. Second Harmonic Generation (SHG) microscopy is a novel technology using multiphoton imaging techniques with applicability in histological tissue assessment. Using an automated algorithm based on signature SHG parameters, we explored the utility and application of SHG for the diagnosis and quantification of HS. SHG microscopy analysis using GENESIS (HistoIndex, Singapore) was applied on 86 archived liver biopsy samples. Reliability was correlated with 3 liver histopathologists. Data analysis was performed using SPSS. There was minimal inter-observer variability between the 3 liver histopathologists, with an intraclass correlation of 0.92 (95% CI 0.89-0.95; p < 0.001). Good correlation was observed between the histopathologists and automated SHG microscopy assessment of HS with Pearson correlation of 0.93: p < 0.001. SHG microscopy provides a valuable tool for objective, more precise measure of HS using an automated approach. Our study reflects proof of concept evidence for potential future refinement to current conventional histological assessment.

Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome.

BACKGROUND: Hepatocellular carcinoma (HCC) is uncommon in young adults. This study examined the clinical characteristics and survival outcome of young HCC patients compared with those in older patients. METHODS: Data were prospectively collected from 638 patients diagnosed with HCC over a 9-year period. Patients aged < or =40 years at diagnosis of HCC were defined as young HCC patients. Their clinical characteristics and survival was compared with those aged >40 years. RESULTS: The prevalence of young HCC was 8.6% (55/638). Young HCC patients had a significantly higher rate of hepatitis B-related disease (HBsAg positivity: 85.5% vs. 59.7%, P = 0.003), better Child-Pugh status (Child-Pugh class A: 69.1% vs. 43.9%, P = 0.002), and lower rates of cirrhosis (12.7% vs. 34.3%, P = 0.001) compared with the older group. They had more advanced disease at diagnosis, with higher alpha-fetoprotein levels (>12 000 microg/l: 45.4% vs. 30.5%, P = 0.026), a higher incidence of portal vein involvement (63.6% vs. 40%, P = 0.003), and a more advanced TNM stage (TNM IV: 83.6% vs. 66.4%, P = 0.018). More young patients were eligible for surgical resection (18.2% vs. 8.2%, P = 0.014). The overall survival between the two groups was similar, but when the patients were stratified for stage of disease, the median survival of young patients with early disease was superior to that of older patients (51.2 vs. 11.6 months, P = 0.025). CONCLUSIONS: HCC in young adults occurs mainly in hepatitis B carriers and is often diagnosed at an advanced stage. Their survival outcome is not different from that of older patients because the advanced disease at presentation offsets the advantages of better liver function and a higher resection rate. However, there is a distinct survival advantage for young patients diagnosed with early disease. These results support the importance of extending HCC surveillance to young hepatitis B carriers.

Second harmonic generation microscopy provides accurate automated staging of liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Assessment of severity of liver fibrosis is essential in the management of non-alcoholic fatty liver disease (NAFLD). Second Harmonic Generation (SHG) microscopy is a novel optical tissue imaging system that provides automated quantification of fibrosis based on unique architectural features of collagen. This study aims to develop and validate a SHG-based index for automated staging of liver fibrosis in patients with NAFLD. METHODS: SHG microscopy was performed on archived liver biopsy specimens from 83 patients with NAFLD. A unique algorithm was developed to identify specific SHG parameters that correlated with fibrosis stage. The accuracy of the algorithm was compared against clinical assessment by experienced liver histopathologists using the Brunt fibrosis staging and further validated using the leave-one-out cross-validation method. RESULTS: Mean age of the study cohort was 51.8 ± 11.7 years, with 41% males. A fibrosis index (SHG B-index) was developed comprising 14 unique SHG-based collagen parameters that correlated with severity of NAFLD fibrosis in a continuous fashion. The SHG B-index had excellent correlation with Brunt fibrosis stage (Spearman's correlation 0.820, p<0.001). AUROCs for prediction of Brunt fibrosis stages 1, 2, 3 and 4 were 0.853, 0.967, 0.985 and 0.941 respectively. In the cross-validation analysis, the SHG B-index demonstrated high specificity for diagnosis of all grades of fibrosis. A SHG B-index score of >1.76 had an overall diagnostic accuracy of 98.5% for prediction of presence of bridging fibrosis (Brunt stage ≥3) with sensitivity of 87.5%, specificity 98.0%, positive predictive value 96.6% and negative predictive value 92.6%. CONCLUSION: The SHG B-index is a unique SHG-based index that provides accurate automated assessment of fibrosis stage in NAFLD patients.