Background/Aims: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). Methods: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC. Results: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. Conclusions MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

In the foot, the lumbricals flex the metatarsophalangeal joints and extend the interphalangeal joints. The lumbricals are known to be affected in neuropathies. It is not known whether they may degenerate in normal individuals. Here, we report our findings of isolated degenerated lumbricals in seemingly normal feet of two cadavers. We explored lumbricals in 20 male and 8 female cadavers that were 60–80 years of age at the time of death. As part of routine dissection, we exposed the tendons of the flexor digitorum longus and the lumbricals. From the degenerated lumbricals, we took some tissue for paraffin-embedding, sectioning, and staining by hematoxylin and eosin, and Masson’s trichrome technique. Of the 224 lumbricals studied, we found four apparently degenerated lumbricals in two male cadavers. In the first, the 2nd and 4th lumbricals in the left foot and the 2nd in the right foot were degenerated. In the second, the right 4th lumbrical was degenerated. Microscopically, the degenerated tissue was made of bundles of collagen. The lumbricals may have degenerated due to compression of their nerve supply. We cannot comment on whether the functionality of the feet were affected by these isolated degeneration of the lumbricals.

“Metabolic dysfunction-associated fatty liver disease (MAFLD)” is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in leanormal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and nonspecialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in leanormal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.

Metabolic (dysfunction) associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease worldwide. Many risk factors contribute to the pathogenesis of MAFLD with metabolic dysregulation being the final arbiter of its development and progression. MAFLD poses a substantial economic burden to societies, which based on current trends is expected to increase over time. Numerous studies have addressed various aspects of MAFLD from its risk associations to its economic and social burden and clinical diagnosis and management, as well as the molecular mechanisms linking MAFLD to end-stage liver disease and hepatocellular carcinoma. This review summarizes current understanding of the pathogenesis of MAFLD and related diseases, particularly liver cancer. Potential therapeutic agents for MAFLD and diagnostic biomarkers are discussed.
Carcinoma, Hepatocellular/complications* ; Humans ; Liver Neoplasms/complications* ; Non-alcoholic Fatty Liver Disease/complications* ; Risk Factors

BACKGROUND/AIMS: Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. METHODS: The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. RESULTS: Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. CONCLUSIONS: Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country.
Cohort Studies ; Hepacivirus ; Hepatitis A virus ; Hepatitis A* ; Hepatitis B ; Hepatitis B virus ; Hepatitis C ; Hepatitis D ; Hepatitis Delta Virus ; Hepatitis Viruses ; Hepatitis* ; Humans ; Incidence ; Infection Control ; Liver Diseases ; Male ; Mongolia* ; Prevalence ; Risk Factors ; Superinfection

BACKGROUND: The Achutha Menon Centre Diabetes Risk Score (AMCDRS), which was developed in rural Kerala State, South India, had not previously been externally validated. We examined the performance of the AMCDRS in urban and rural areas in the district of Vellore in the South Indian state of Tamil Nadu, and compared it with other diabetes risk scores developed from India. METHODS: We used the data from 4,896 participants (30 to 64 years) of a cross-sectional study conducted in Vellore (2010 to 2012), to calculate the AMCDRS scores using age, family history, and waist circumference. Sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), and the area under the receiver operating characteristic curve (AROC) were calculated for undiagnosed and total diabetes. RESULTS: Of the 4,896 individuals surveyed, 274 (5.6%) had undiagnosed diabetes and 759 (15.5%) had total diabetes. The AMCDRS, with an optimum cut-point of ≥4, identified 45.0% for further testing with 59.5% sensitivity, 60.5% specificity, 9.1% PPV, 95.8% NPV, and an AROC of 0.639 (95% confidence interval [CI], 0.608 to 0.670) for undiagnosed diabetes. The corresponding figures for total diabetes were 75.1%, 60.5%, 25.9%, 93.0%, and 0.731 (95% CI, 0.713 to 0.750), respectively. The AROC for the AMCDRS was not significantly different from that of the Indian Diabetes Risk Score, the Ramachandran or the Chaturvedi risk scores for total diabetes, but was significantly lower than the AROC of the Chaturvedi score for undiagnosed diabetes. CONCLUSION: The AMCDRS is a simple diabetes risk score that can be used to screen for undiagnosed and total diabetes in low-resource primary care settings in India. However, it probably requires recalibration to improve its performance for undiagnosed diabetes.
Cross-Sectional Studies ; Humans ; India* ; Primary Health Care ; ROC Curve ; Sensitivity and Specificity ; Waist Circumference