Mistakes in managing hepatocellular carcinoma and how to avoid them: a narrative review.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common liver-related cancer and the third leading cause of worldwide cancer-related mortality. AREAS COVERED: There have been many updated guidelines on the management of HCC in the past few years. Given the increasing burden of HCC in clinical practice, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with HCC. Early detection and judicious treatment based on the stage of the HCC can improve patient outcomes. We performed a PubMed (MEDLINE database) search for the latest guidelines related to the screening, detection, diagnosis, staging, and management of HCC. We aim to highlight some major considerations and common mistakes in managing HCC and attempt to provide evidence-based recommendations. EXPERT OPINION: The field of HCC management is expected to evolve in the coming years. Increased emphasis on personalized treatment and precision medicine with earlier detection methods, the development of noninvasive diagnostic tools, increased focus on combination therapies and a shift toward more targeted treatments will become more critical.

Prevalence and associated factors for non-alcoholic fatty liver disease among adults in the South Asian Region: a meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease worldwide. We estimated the prevalence and predefined associated factors for NAFLD among South-Asian adults. Methods: We searched PubMed and included descriptive, epidemiological studies with satisfactory methodology, reporting the prevalence of NAFLD with ultrasound. Two authors screened and extracted data independently. Gender, urban/rural settings, general population and individuals with metabolic diseases (MetD) stratified the analysis. In addition, a random-effects meta-analysis of the prevalence and effect sizes of associations of NAFLD was performed. Findings: Twenty-two publications were included after the quality assurance process. The difference in the NAFLD prevalence between the general population and people with MetD was found to be statistically significant (Q = 15.8, DF = 1, P < 0.001). The pooled overall prevalence of NAFLD in the general population was 26.9% (95% CI: 18.9-35.8%) with high heterogeneity. The prevalence was similar among men and women (Q = 0.06, DF = 1, P = 0.806). The NAFLD prevalence in the rural communities was 22.6% (95% CI: 13.6-33.1%), and the prevalence in urban communities was 32.9% (95% CI: 22.8-43.8%) and the difference was not statistically significant (Q = 1.92, DF = 1, P = 0.166). The pooled overall prevalence of NAFLD in patients with MetD was 54.1% (95% CI: 44.1-63.9%) with high heterogeneity. The pooled overall prevalence of NAFLD in the non-obese population was 11.7% (95% CI: 7.0-17.3%). The pooled prevalence of non-obese NAFLD in the NAFLD population was 43.4% (95% CI: 28.1-59.4%). Meta-analysis of binary variables showed that NAFLD in the South Asian population was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity and metabolic syndrome. Gender was not associated with NAFLD. Interpretation: The overall prevalence of NAFLD among adults in South Asia is high, especially in those with MetD, and a considerable proportion is non-obese. In the South Asian population, NAFLD was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity, and metabolic syndrome. Funding: None.

'Mistakes in managing non-alcoholic fatty liver disease and how to avoid them'.

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease. NAFLD is estimated to affect 25% of the global population. Therefore, it is widely encountered in primary care. A proportion of patients with NAFLD need a specialist referral, evaluation and follow-up.There have been many updated guidelines on the management of NAFLD in the past few years. Given the burden of NAFLD in the community and its cardiovascular and liver-related adverse outcomes, knowledge of evidence-based standards of care for these patients is essential for any practitioner managing patients with NAFLD. As an asymptomatic disease in the early stages, NAFLD can lead to many mistakes in its management.We aim to highlight some common mistakes in managing NAFLD and attempt to provide evidence-based recommendations.

The association between steatosis and liver damage in transfusion-dependent beta thalassaemia patients.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Iron is the leading cause of liver damage in patients with transfusion-dependent thalassaemia (TDT), and data on the contribution of NAFLD to liver damage in TDT is lacking. Forty-five heavily transfused TDT patients who did not have biochemical or ultrasonic evidence of liver cirrhosis were evaluated for effects of iron overload, including the presence of diabetes mellitus, hypogonadism, serum ferritin, R2-MRI-liver, and liver enzymes alanine aminotransferase and aspartate aminotransferase. Liver fibrosis and steatosis were estimated using transient elastography (TE). Nine (20%) patients had significant steatosis (S1), and their body mass index (BMI) and liver fibrosis scores were higher than in patients without significant steatosis (S0) (p = 0.03 and p = 0.004, respectively). On regression analysis, the controlled attenuation parameter (CAP) score (i.e., degree of liver steatosis) was associated only with increasing BMI. The TE score (i.e., degree of liver fibrosis) was associated with increasing age, CAP score, male gender, and presence of diabetes. Neither liver steatosis nor fibrosis showed significant association with the liver iron concentration or iron-related organ damage (hypogonadism). In this cohort of TDT patients, steatosis of the liver, which is associated with increasing BMI, appeared to increase the risk of liver fibrosis.

AARC score determines outcomes in patients with alcohol-associated hepatitis: a multinational study.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients. METHODS: Prospectively collected data from the AARC database were analyzed. RESULTS: Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p < 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p < 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores. CONCLUSION: Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion-dependent beta thalassaemia: a cross-sectional study.

OBJECTIVE: To evaluate the performance of the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis (F2) compared with transient elastography (TE), among chronic transfusion-dependent beta-thalassaemia (TDT) patients in a resource-poor setting. DESIGN: A cross-sectional study. SETTING: Adolescent and Adult Thalassaemia Care Centre (University Medical Unit), Kiribathgoda, Sri Lanka. PARTICIPANTS: 45 TDT patients who had undergone more than 100 blood transfusions with elevated serum ferritin >2000 ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibodies were excluded. OUTCOME MEASURES: TE and FIB-4 scores were estimated at the time of recruitment in all participants. Predefined cut-off values for F2, extracted from previous TE and FIB-4 scores studies, were compared. A new cut-off value for the FIB-4 score was estimated using receiver operating characteristics curve analysis to improve the sensitivity for F2 prediction. RESULTS: Of the selected 45 TDT patients, 22 (49%) were males. FIB-4 score showed a significant linear correlation with TE (r=0.52;p<0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand, it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4, we improved the pick-up rate of F2 to 72%. CONCLUSIONS: Regardless of the cut-off point, the FIB-4 score cannot be used as a good screening tool to pick up F2 in patients with TDT, irrespective of their splenectomy status. On the contrary, at a 1.3 cut-off value, though FIB-4 is a very poor detector for F2 fibrosis, it will not erroneously diagnose F2 fibrosis in those who do not have it.

Chronic nausea and vomiting: a diagnostic approach.

INTRODUCTION: Chronic nausea and vomiting (CNV) are commonly encountered symptoms in medical practice. CNV is the presenting symptom in a variety of gastrointestinal and non-gastrointestinal disorders. However, in a significant percentage of patients without an obvious underlying cause, CNV poses a significant diagnostic challenge to the evaluating physician. AREAS COVERED: A comprehensive clinical history and physical examination form the foundation for further diagnostic work-up. In the present review, we discuss the diagnostic approach to CNV, highlighting the epidemiology, pathophysiology, causes, and modes of evaluation of this condition. Specific investigations, carefully guided by clinical assessment and tailored for each patient, would be more beneficial in diagnosing CNV than empirically performing a blanket of investigations. EXPERT OPINION: Whilst CNV remains a historically challenging diagnostic and therapeutic dilemma, research into this topic is limited. Hence, there is a growing call for more research into diagnostic modalities for CNV. With scientific advancement and further research, it is hoped that easy-to-use, cheap, noninvasive novel diagnostic modalities for CNV will be available soon.

Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy.

Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Late-onset neurodegenerative manifestations in patients with cirrhosis: acquired hepatocerebral degeneration - a neglected diagnosis.

Acquired hepatocerebral degeneration (AHCD) is an acquired, extrapyramidal, neurodegenerative condition, encountered in patients with cirrhosis. It is an uncommon and usually irreversible condition, resulting in widespread cerebral, basal ganglia and cerebellar damage. We describe here four cases of AHCD, with varying presentations, highlighting the need for increased awareness of this condition, to avoid diagnostics delays and unnecessary management.

Incidence and prevalence of alcoholic fatty liver disease: a prospective, community-based study among adult Sri Lankans.

Background: Data on the alcoholic fatty liver (AFL) is limited. Therefore, we investigated alcohol use and AFL patterns among urban, adult Sri Lankans. Methods: The study population (selected by age-stratified random sampling) was screened in 2007 (35-64 years) and re-evaluated in 2014. They were assessed by structured interviews, anthropometric measurements, liver-ultrasound, and biochemical and serological tests. AFL was diagnosed on ultrasound criteria, 'unsafe' alcohol consumption (Asian standards: males>14units, females>7units per week) and absence of hepatitis B/C markers. Controls were unsafe alcohol consumers who had no fatty liver on ultrasound. Results: 2985/3012 (99%) had complete data for analysis. 272/2985 (9.1%) were unsafe-drinkers in 2007 [males-270; mean-age-51.9, SD-8.0 years]. 86/272 (31.6%) had AFL [males-85; mean-age-50.2, SD-8.6 years]. Males [p<0.001], increased waist circumference (WC) [OR 4.9, p<0.01] and BMI>23kg/m2 [OR 3.5, p<0.01] and raised alanine aminotransferase (ALT) [OR 2.8, p<0.01] were independently associated with AFL. 173/272 (63.6%) unsafe alcohol consumers from 2007 were re-evaluated in 2014. 134/173 had either had AFL or had changed to 'safe' or no alcohol consumption. 21/39 (53.8%) [males-21 (100%), mean-age-57.9, SD-7.9 years] who remained 'unsafe' alcohol users who had no fatty liver in 2007 developed AFL after 7-years (annual incidence 7.7%). On bivariate analysis, only males were associated with new-onset AFL. Of the 42 who had AFL at baseline but changed their drinking status from unsafe to safe or no alcohol, 6 had resolution of fatty liver in 2014. Conclusion: In conclusion, in this community-based study among urban Sri Lankan adults, the annual incidence of AFL among unsafe alcohol users was 7.7%. Furthermore, new-onset AFL was associated with males.

The use of personal protective equipment in endoscopy: what should the endoscopist wear during a pandemic?

Endoscopists are at high risk of exposure and nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) when performing endoscopic procedures due to the highly aerosol generating nature of these procedures. At present, there is still no consensus among endoscopists with regards to the type of protective equipment to be worn by healthcare workers, when performing endoscopy during the coronavirus 2019 (COVID-19) pandemic. This review encompasses a summary of currently published guidelines related to the use of personal protective equipment (PPE) when performing endoscopic procedures during the COVID-19 pandemic. With increasing calls to rationalize the use of PPE due to shortages in global supply chains, the review offers a concise summary on the most appropriate and adequate use of PPE when performing endoscopy during the pandemic. It is expected that these adaptations in the use of PPE during the pandemic will help to improve standards of care and safety of healthcare workers.

Outcomes of NAFLD and MAFLD: Results from a community-based, prospective cohort study.

BACKGROUND: The term "metabolic (dysfunction)-associated fatty liver disease" (MAFLD) is suggested alternative for "non-alcoholic fatty liver disease" (NAFLD), as it better reflects metabolic dysfunction. No study has compared outcomes of the two diagnostic criteria. METHODS: In an ongoing, community-based, cohort-study in suburban Sri Lanka, participants were randomly selected in 2007. They were reassessed in 2014 to evaluate new-onset metabolic traits (MTs) and cardiovascular-events (CVEs). Baseline characteristics, MTs and CVEs after 7-years were compared in NAFLD and MAFLD and vs. controls. Similarly, we compared these parameters in those excluded by the NAFLD definition but captured by the MAFLD definition and vice versa, and vs. controls. FINDINGS: Of 2985 recruited in 2007, 940 (31.5%) had NAFLD, 990 (33.1%) had MAFLD and 362 (12.1%) were controls. When compared to NAFLD, MAFLD captured an additional 2.9% and lost 1.3% individuals. At baseline, anthropometric and metabolic traits were similar in NAFLD and MAFLD. At follow-up in 7-years, the risk of having new-onset MTs and fatal/non-fatal CVEs were similar in the groups, but were significantly higher compared to controls. Those excluded by the NAFLD definition but captured by the MAFLD definition showed higher baseline MTs compared to those excluded by the MAFLD definition but captured by the NAFLD definition, and had substantially higher risk for having new-onset MTs and CVEs compared to controls. INTERPRETATION: Although NAFLD and MAFLD had similar MTs at baseline, and similar outcomes after 7-years, those who were excluded by the NAFLD definition but captured by the MAFLD definition seem at higher risk of adverse outcomes than those excluded by the MAFLD definition but captured by the NAFLD definition. Although the increase in the index population was small, redefining NAFLD as MAFLD seemed to improve clinical utility.

The clinical utility of accurate NAFLD ultrasound grading: Results from a community-based, prospective cohort study.

OBJECTIVES: Despite its widespread use there is no consensus on ultrasound criteria to diagnose fatty liver. METHOD: In an ongoing, cohort-study, participants were initially screened in 2007 and reassessed in 2014 by interview, anthropometric measurements, liver ultrasonography, and blood tests. We evaluated utility of increased hepatic echogenicity alone (intermediate) compared to using additional criteria which included signal attenuation and/or vascular blunting along with increase of hepatic echogenicity (moderate-severe), to diagnose fatty liver in NAFLD. We made a comparison of the two radiologically defined groups, in order to choose a classification method for NAFLD, which may better predict baseline adverse metabolic traits (MT), and adverse metabolic and cardiovascular events (CVE) after 7-year of follow-up. RESULTS: Of 2985 recruited in 2007, 940 (31.5 %) had moderate-severe NAFLD, 595 (19.9 %) intermediate NAFLD, and 957 (32.1 %) were controls (no fatty liver). 2148 (71.9 %) attended follow-up in 2014; they included 708 who had moderate-severe NAFLD, 446 intermediate NAFLD and 674 controls, at baseline (in 2007). At baseline, adverse anthropometric indices and MTs were significantly higher in both moderate-severe NAFLD and intermediate NAFLD compared to controls, except for low HDL. They were commoner in moderate-severe NAFLD than in intermediate NAFLD. After seven years, the odds of developing new-onset metabolic traits and CVEs were significantly higher compared to controls only in moderate-severe NAFLD. CONCLUSIONS: Only moderate-severe NAFLD predicted risk of incident adverse MTs and CVEs. However, both moderate-severe and intermediate NAFLD were associated with higher prevalence of adverse anthropometric and metabolic traits, thereby identifying individuals who need medical intervention even among those with milder degrees of fatty liver. We therefore recommend using increased hepatic echogenicity, and not only the more stringent criteria (which include signal attenuation and/or vascular blunting), for the diagnosis of fatty liver in individuals with NAFLD.

Masks in COVID-19: let's unmask the evidence.

INTRODUCTION: One of the main issues in the novel coronavirus 2019 (COVID-19) pandemic has been the lack of uniformity of recommendations for the usage of face masks. AREAS COVERED: While Asian countries started using masks early during the epidemic, most Western countries were slow to do so. To avoid such situations, clear guidelines, need to be established, not only regarding the use of masks but also the type of mask to suit different situations. In this article, we will examine the types of masks and review the recommendations for their use based on the available evidence for each type of mask. EXPERT OPINION: We explore future needs in research-related mask use in COVID-19 pandemic, improvements to be made in mask design, adopting guidelines for the use of masks and the psycho-social aspects of widespread and prolonged mask use.