Metabolic dysfunction-associated fatty liver disease: a year in review.

PURPOSE OF REVIEW: In 2020, a novel comprehensive redefinition of fatty liver disease was proposed by an international panel of experts. This review aims to explore current evidence regarding the impact of this new definition on the current understanding of the epidemiology, pathogenesis, diagnosis, and clinical trials for fatty liver disease. RECENT FINDINGS: The effectiveness of metabolic dysfunction-associated fatty liver disease (MAFLD) was compared to the existing criteria for nonalcoholic fatty liver disease (NAFLD). Recent data robustly suggest the superior utility of MAFLD in identifying patients at high risk for metabolic dysfunction, the hepatic and extra-hepatic complications, as well as those who would benefit from genetic testing, including patients with concomitant liver diseases. This change in name and criteria also appears to have improved disease awareness among patients and physicians. SUMMARY: The transformation in name and definition from NAFLD to MAFLD represents an important milestone, which indicates significant tangible progress towards a more inclusive, equitable, and patient-centred approach to addressing the profound challenges of this disease. Growing evidence has illustrated the broader and specific contexts that have tremendous potential for positively influencing the diagnosis and treatment. In addition, the momentum accompanying this name change has included widespread public attention to the unique burden of this previously underappreciated disease.

Effects of coronavirus disease 2019 on the digestive system and its nutritional implications.

PURPOSE OF REVIEW: There has been a deluge of scientific data since coronavirus disease 2019 (COVID-19) was first reported. The effects of COVID-19 on the digestive system are now increasingly well understood. This article aims to review the current data on the effects of COVID-19 on the digestive system with particular emphasis on preexisting digestive diseases and its implications on nutrition practices. RECENT FINDINGS: Evidence has shown that Severe acute respiratory syndrome coronavirus 2 virus affects the gastrointestinal (GI) tract, pancreas and hepatobiliary system resulting in different GI manifestations. Several preexisting digestive diseases have been investigated. These studies have revealed that these special patient population groups are generally not at an increased risk to contract COVID-19, but are susceptible to develop increasing severity of disease. Aside from medical therapy, optimizing nutritional care has a beneficial role in this group of patients. SUMMARY: GI manifestations of COVID-19 in addition to preexisting digestive diseases have an impact on patient's nutrition. Digestion, absorption and transport of nutrients may be impaired. To date, there are no existing guidelines on the nutritional management of patients for this particular at-risk group. Most nutrition practices are based only on observations and clinical experience. Basic prepandemic nutrition care principles are primarily followed but often individualized based on clinical judgment.

Budd-Chiari syndrome: consensus guidance of the Asian Pacific Association for the study of the liver (APASL).

Budd Chiari syndrome (BCS) is a diverse disease with regard to the site of obstruction, the predisposing thrombophilic disorders and clinical presentation across the Asia-Pacific region. The hepatic vein ostial stenosis and short segment thrombosis are common in some parts of Asia-Pacific region, while membranous obstruction of the vena cava is common in some and complete thrombosis of hepatic veins in others. Prevalence of myeloproliferative neoplasms and other thrombophilic disorders in BCS varies from region to region and with different sites of obstruction. This heterogeneity also raises several issues and dilemmas in evaluation and approach to management of a patient with BCS. The opportunity to recanalize hepatic vein in patients with hepatic vein ostial stenosis or inferior vena cava stenting or pasty among those membranous obstruction of the vena cava is a unique opportunity in the Asia-Pacific region to restore hepatic outflow closely mimicking physiology. In order to address these issues arising out of the diversity as well as the unique features in the region, the Asia Pacific Association for Study of Liver has formulated these guidelines for clinicians.

Association of metabolic-associated fatty liver disease and risk of severe coronavirus disease 2019 illness.

Given the global health burden caused by the Coronavirus Disease 2019 (COVID-19), there have been numerous studies aimed to understand its clinical course and to determine risk factors that may impact prognosis. Pre-existing medical conditions are linked with COVID-19 severity, particularly cardiometabolic diseases. Increasing evidence has also linked metabolic-associated fatty liver disease (MAFLD) with severe COVID-19 illness. Thus, we review different published clinical data relating to the association of MAFLD and COVID-19 severity. Our review showed that published studies consistently support the association between MAFLD and more severe COVID-19, even after adjustment for confounding factors. It was also observed that an increasing hepatic fibrosis score is correlated with increasing severity of COVID-19. Finally, younger age and obesity among MAFLD patients also led to a greater risk of severe illness.

Moving Forward: Gradual Return of Gastroenterology Practice during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has caused disruption of routine gastroenterology practice, which has resulted in the suspension of elective endoscopic procedures and outpatient consults. For the past months, the strategy was to mitigate infection risk for the healthcare team while still providing essential service to patients. Prolonged suspension of the outpatient clinics and endoscopy practice, however, is deemed unsustainable and could even be detrimental. It can compromise patient care and result in poor outcomes; hence, a well-crafted plan is needed for the gradual resumption of clinic operations and endoscopic procedures. SUMMARY: As the world begins to transition to the "new normal," there are new health and safety issues to consider. Adaptive measures like telemedicine and electronic health records should be utilized to facilitate patient care while minimizing exposure. Careful patient screening, adequate supply of personal protective equipment, effective infection-control policies, as well as appropriate administrative modifications are needed for a safe return of gastroenterology practice. Key Messages: Ensuring the safety of patients, caregivers, and healthcare workers should remain as top priority. To help ease the transition as we move forward from this pandemic, we present a review of recommendations to guide gastroenterologists and endoscopy unit administrators in the gradual return to gastroenterology practice.

The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.

An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia.

Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.

Gastrointestinal Manifestations of COVID-19: Impact on Nutrition Practices.

Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease, growing evidence shows that it can affect the digestive system and present with gastrointestinal (GI) symptoms. Various nutrition societies have recently published their guidelines in context of the pandemic, and several points emphasize the impact of these GI manifestations on nutrition therapy. In patients with COVID-19, the normal intestinal mucosa can be disrupted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and this could result in GI symptoms and a compromise in nutrient absorption. Optimization of oral diet is still recommended. However, given the GI effects of COVID-19, a fraction of infected patients have poor appetite and would not be able to meet their nutrition goals with oral diet alone. For this at-risk group, which includes those who are critically ill, enteral nutrition is the preferred route to promote gut integrity and immune function. In carrying this out, nutrition support practices have been revised in such ways to mitigate viral transmission and adapt to the pandemic. All measures in the GI and nutrition care of patients are clustered to limit exposure of healthcare workers. Among patients admitted to intensive care units, a significant barrier is GI intolerance, and it appears to be exacerbated by significant GI involvement specific to the SARS-CoV-2 infection. Nevertheless, several countermeasures can be used to ease side effects. At the end of the spectrum in which intolerance persists, the threshold for switching to parenteral nutrition may need to be lowered.

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).

BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

COVID-19 and its effects on the digestive system and endoscopy practice.

The Coronavirus Disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been classified as a pandemic by the World Health Organization in March 2020. Several studies have demonstrated that the gastrointestinal (GI) tract is also a potential route. As the pandemic is continuously evolving, and more data are made available, this article highlights the best evidence and practices regarding the effects of the SARS-CoV-2 virus relevant to GI practice. Published clinical studies have supported that SARS-CoV-2 affects the GI tract and the liver. The largest published dataset comprised of 4243 patients and showed a pooled prevalence of GI symptoms at 17.6%. GI symptoms varied and usually preceded pulmonary symptoms by 1-2 days. These include anorexia (26.8%), nausea and vomiting (10.2%), diarrhea (12.5%), and abdominal pain (9.2%). Incidence of liver injury ranges from 15 to 53%. Evidence shows that the severity of COVID-19 infection is compounded by its effects on nutrition, most especially for the critically ill. As such, nutrition societies have recommended optimization of oral diets and oral nutritional supplements followed by early enteral nutrition if nutritional targets are not met, and parenteral nutrition in the distal end of the spectrum. In addition to possible fecal-oral transmission, GI endoscopy procedures, which are considered to be aerosol-generating procedures, contribute to increased risk to GI health-care professionals. Infection prevention measures and guidelines are essential in protecting both patients and personnel.

Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

The 2014 Hepatology Society of the Philippines consensus statements on the diagnosis and treatment of hepatitis C

Hepatitis C virus (HCV) infection is a devastating disease that is increasingly being diagnosed among Filipinos, especially in at-risk populations. There are disease-specific nuances in the evaluation and management of this infection. Furthermore, advances in the field brought about by clinical research are rapidly moulding the way we evaluate and manage HCV patients. Evidently, consensus statements formulated by experts in the field are needed in order to serve as a guide to physicians who see HCV patients in the clinic. With this in mind, the Hepatology Society of the Philippines spearheaded the formation of these statements which aimed to address issues in the diagnosis, evaluation, treatment, and follow-up care of patients with HCV infection.Recommendations on the specific tests to perform in the evaluation of HCV patients before, during and after treatment, and first-line treatment of patients with acute and chronic HCV infection were provided. Treatment algorithms for chronic HCV infection, divided according to viral genotype, were also devised. We acknowledge the limitations brought about by the local inavailability of some drugs/treatment regimens in the local setting at the time of the formulation of these statements. As such, these statements will be revised as soon as new data become locally applicable.  

Genotype-specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C.

UNLABELLED: The interaction between insulin resistance (IR), steatosis and genotype to fibrosis in chronic hepatitis C virus (HCV) infection has not been comprehensively assessed. We hypothesized that IR is a key mediator for the development of both steatosis and fibrosis in 346 untreated, nondiabetic patients solely infected with either genotype 1 or 3. We examined for genotype-specific interactions between IR, steatosis and fibrosis by performing subgroup analyses. Because cirrhosis is known to cause IR, we repeated the analysis in a cohort of 313 noncirrhotic HCV-infected patients. We confirmed the impact of IR on fibrosis by analysis of 153 lean subjects in whom any effect of steatosis would be minimized. In HCV genotype 3 patients, increased steatosis was linked to high viral load (P = 0.001), and was not associated with fibrosis (P = 0.1). In contrast, body mass index (P = 0.04) and homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.01) contributed directly to steatosis in HCV genotype 1. HOMA-IR rather than steatosis was independently associated with fibrosis for both HCV genotype 1 (OR, 3.22; P = 0.02) and genotype 3 (OR, 3.17; P = 0.04). Exclusion of cirrhotic subjects did not alter the findings with respect to the greater contribution of IR compared to hepatic steatosis, as a predictor of fibrosis (P = 0.02). Genotype-specific subgroup analyses did not alter this finding. The extent of HOMA-IR remained significantly associated with fibrosis in lean patients, independent of the confounding effect of body mass index on IR (OR, 8.02; P = 0.003). CONCLUSION: IR is a major independent determinant of fibrosis in chronic HCV infection, regardless of the genotype and the severity of liver damage.

Combined percutaneous radiofrequency ablation and ethanol injection for hepatocellular carcinoma in high-risk locations.

OBJECTIVE: The purpose of this study was to investigate whether combining percutaneous ethanol injection (PEI) with radiofrequency ablation in the management of hepatocellular carcinoma (HCC) in high-risk locations improves treatment outcomes. SUBJECTS AND METHODS: We compared the outcome of management of high-risk tumors with PEI and radiofrequency ablation (n = 50) or radiofrequency ablation alone (n = 114) with the outcome of radiofrequency ablation of non-high-risk tumors (n = 44). We also compared the survival rates of patients with and those without high-risk HCC. PEI was performed into the part of the tumor closest to a blood vessel or vital structure before radiofrequency ablation. RESULTS: The study included 142 patients with 208 HCCs managed with radiofrequency ablation. Despite larger tumor sizes (2.8 +/- 1 cm vs 1.9 +/- 0.7 cm vs 2.5 +/- 0.1 cm for the high-risk radiofrequency plus PEI, non-high-risk radiofrequency, and high-risk radiofrequency groups, respectively; p < 0.001), the primary effectiveness rate of high-risk radiofrequency ablation and PEI (92%) was similar to that of non-high-risk radiofrequency ablation (96%). The primary effectiveness rate of high-risk radiofrequency ablation and PEI was slightly higher (p = 0.1) than that of high-risk radiofrequency ablation (85%). The local tumor progression rates (21% vs 33% vs 24% at 18 months) of the three respective groups were not statistically different (p = 0.91). Patients with and those without high-risk tumors had equal survival rates (p = 0.42) after 12 (87% vs 100%) and 24 (77% vs 80%) months of follow-up. Independent predictors of primary effectiveness were a tumor size of 3 cm or less (p = 0.01) and distinct tumor borders (p = 0.009). Indistinct borders (p = 0.033) and non-treatment-naive status of HCC (p = 0.002) were associated with higher local tumor progression rates. The only predictor of survival was complete ablation of all index tumors (p = 0.001). CONCLUSION: The combination of radiofrequency ablation and PEI in the management of HCC in high-risk locations has a slightly higher primary effectiveness rate than does radiofrequency ablation alone. A randomized controlled study is warranted.

Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3.

BACKGROUND/AIMS: Obesity is associated with impaired treatment responses in chronic hepatitis C. The aim of this study was to determine the relationship between the insulin resistance frequently seen in obese subjects and sustained virological response to anti-viral therapy (SVR) in patients with genotype 2 or 3 infection. METHODS: Eighty-two patients were studied; 59 received interferon/ribavirin while 23 received peg-interferon/ribavirin. RESULTS: The overall SVR was (77%). Patients with a SVR had lower mean serum insulin (10.7+/-0.8 microU/ml vs. 22.2+/-4.9; P = 0.03), fibrosis stage (1.9+/-0.1 vs. 2.7+/-0.3; P = 0.007) and insulin resistance measured by the homeostasis model (HOMA-IR) (2.5+/-0.2 vs. 6.1+/-1.5; P = 0.03). Age, gender, ethnicity, alcohol consumption, treatment regimen, viral load, portal activity and steatosis did not influence the SVR. By linear regression, body mass index (P < 0.001) and fibrosis stage (P < 0.001) were independently associated with HOMA-IR. After adjusting for fibrosis stage, patients with HOMA-IR of < 2 were 6.5 times more likely to achieve SVR than those with HOMA-IR > or = 2. CONCLUSIONS: Even in treatment-responsive genotypes 2 and 3, high HOMA-IR is associated with a reduced response. Improving insulin sensitivity may be a useful adjunct to anti-viral therapy in these individuals.

Treatment of hepatocellular carcinoma using internally cooled electrodes. A prospective comparison of modified automated vs. manual pulsed radiofrequency algorithms.

OBJECTIVES: To compare the effectiveness of modified automated and manual pulsed radiofrequency (RF) algorithms using internally cooled electrodes for hepatocellular carcinoma (HCC). METHODS: Seventy-seven treatment-naive cirrhotic patients with 102 HCC (< or =4 cm) underwent 109 sessions of ultrasound-guided percutaneous RF ablation using a 17-gauge, 20-cm-long, single internally cooled electrode. Patients were assigned alternatively: 40 patients to the modified automated algorithm group and 37 patients to the manual algorithm group. The mean tumor diameters were 2.34 +/- 0.9 and 2.25 +/- 0.7 cm in the automated and manual groups, respectively (p = 0.56). Primary technique effectiveness and local tumor progression were compared between the two groups. RESULTS: More overlapping ablations (n = 112) were required in the manual than in the automated group (n = 82) to achieve similar primary technique effectiveness rates of 96.1 and 94.1%, respectively. After a mean follow-up period of 26.7 +/- 1.1 months, the local tumor progression rates at 12 and 18 months were 4 and 20% in the manual group and 12 and 24% in the modified automated group (p = 0.3). Only tumors >3 cm were independently associated with local tumor progression (odds ratio 1.25; 95% CI 1.06-2.34, p = 0.03). CONCLUSIONS: The manual algorithm requires more overlapping ablations and treatment sessions in order to achieve similar primary technique effectiveness and local tumor progression rates compared with the modified automated algorithm.