UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis.
UNASSIGNED: Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies.
UNASSIGNED: A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 ± 8.5 months in pediatrics to 58.90 ± 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 ± 0.08 to 1.3 ± 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 ± 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls.
UNASSIGNED: The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.

Close follow-up of patients with liver cirrhosis has led to increased detection of hepatocellular carcinoma (HCC) at an early stage, especially with magnetic resonance imaging (MRI) innovations. We report the case of a 70-year-old man, with a recent history of liver cirrhosis due to chronic hepatitis C virus (HCV) complicated by hepatocellular carcinoma (HCC), and for whom trans-arterial chemoembolization (TACE) was planned, as the patient was assigned Child B7 at admission. Angiography performed during the first TACE cycle shows not only the \"tumor blush\" corresponding to previously detected HCC but also an additional small foci of HCC uptake seen within a large dysplastic nodule giving the appearance of \"nodule-within-nodule.\" Early detection of hepatocellular carcinoma improves prognosis. Hence, it is essential to be aware of all early aspects of HCC, including the nodule-within-nodule appearance on cross-sectional imaging, and also in angiography, as in this case.

UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) contributes to a large proportion of liver disease burden in the world. Several groups have studied the prevalence of NAFLD in the Indian population.
UNASSIGNED: A systematic review of the published literature and meta-analysis was carried out to estimate the prevalence of NAFLD in the Indian population.
UNASSIGNED: English language literature published until April 2021 was searched from electronic databases. Original data published in any form which had reported NAFLD prevalence in the Indian population were included. The subgroup analysis of prevalence was done based on the age (adults or children) and risk category, i.e., average-risk group (community population, participants of control arm, unselected participants, hypothyroidic individuals, athletes, aviation crew, and army personnel) and high-risk group (obesity or overweight, diabetes mellitus, coronary artery disease, etc.). The prevalence estimates were pooled using the random-effects model. Heterogeneity was assessed with I2.
UNASSIGNED: Sixty-two datasets (children 8 and adults 54) from 50 studies were included. The pooled prevalence of NAFLD was estimated from 2903 children and 23,581 adult participants. Among adults, the estimated pooled prevalence was 38.6% (95% CI 32-45.5). The NAFLD prevalence in average-risk and high-risk subgroups was estimated to be 28.1% (95% CI 20.8-36) and 52.8% (95% CI 46.5-59.1), respectively. The estimated NAFLD prevalence was higher in hospital-based data (40.8% [95% CI 32.6-49.3%]) than community-based data (28.2% [95% CI 16.9-41%]). Among children, the estimated pooled prevalence was 35.4% (95% CI 18.2-54.7). The prevalence among non-obese and obese children was 12.4 (95% CI 4.4-23.5) and 63.4 (95% CI 59.4-67.3), respectively.
UNASSIGNED: Available data suggest that approximately one in three adults or children have NAFLD in India.

BACKGROUND: A deficiency of glycogen debrancher enzyme in patients with glycogen storage disease type III (GSD III) manifests with hepatic, cardiac, and muscle involvement in the most common subtype (type a), or with only hepatic involvement in patients with GSD IIIb.
OBJECTIVE: To describe longitudinal biochemical, radiological, muscle strength and ambulation, liver histopathological findings, and clinical outcomes in adults (≥18 years) with glycogen storage disease type III, by a retrospective review of medical records.
RESULTS: Twenty-one adults with GSD IIIa (14 F & 7 M) and four with GSD IIIb (1 F & 3 M) were included in this natural history study. At the most recent visit, the median (range) age and follow-up time were 36 (19-68) and 16 years (0-41), respectively. For the entire cohort: 40% had documented hypoglycemic episodes in adulthood; hepatomegaly and cirrhosis were the most common radiological findings; and 28% developed decompensated liver disease and portal hypertension, the latter being more prevalent in older patients. In the GSD IIIa group, muscle weakness was a major feature, noted in 89% of the GSD IIIa cohort, a third of whom depended on a wheelchair or an assistive walking device. Older individuals tended to show more severe muscle weakness and mobility limitations, compared with younger adults. Asymptomatic left ventricular hypertrophy (LVH) was the most common cardiac manifestation, present in 43%. Symptomatic cardiomyopathy and reduced ejection fraction was evident in 10%. Finally, a urinary biomarker of glycogen storage (Glc4) was significantly associated with AST, ALT and CK.
CONCLUSIONS: GSD III is a multisystem disorder in which a multidisciplinary approach with regular clinical, biochemical, radiological and functional (physical therapy assessment) follow-up is required. Despite dietary modification, hepatic and myopathic disease progression is evident in adults, with muscle weakness as the major cause of morbidity. Consequently, definitive therapies that address the underlying cause of the disease to correct both liver and muscle are needed.

UNASSIGNED: Individuals with type 2 diabetes (T2DM) are at high risk of developing non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis/cirrhosis. Screening patients with T2DM and normal liver enzymes for NAFLD in primary care remains contentious. Our aim was to develop and assess a primary care pathway integrating two-tier (Fib-4 then transient elastography [TE]) liver fibrosis assessment, irrespective of aetiology, into routine annual review of all patients with T2DM.
UNASSIGNED: All patients aged >35 years with T2DM attending annual review at 2 primary care practices in North East England between April 2018 and September 2019 (n = 467) had Fib-4 requested via the electronic patient record. Those with a Fib-4 score above the \'high-sensitivity\' threshold (>1.3 for ≤65 years and >2.0 for >65 years) underwent TE and were reviewed in secondary care if the liver stiffness measurement (LSM) was >8 kPa. The number of patients identified with advanced disease, service uptake, and predictors of advanced disease were assessed.
UNASSIGNED: A total of 85/467 (18.5%) patients had raised Fib-4; 27/467(5.8%) were excluded as a result of frailty or known cirrhosis. A total of 58/467 (12.2%) were referred for TE. Twenty-five of 58 (43.1%) had an LSM of >8 kPa and 13/58 (22.4%) had an LSM >15 kPa; 4/58 (6.7%) did not attend and 5/58 (9.3%) had an invalid reading. Twenty of 440 (4.5%) patients were found to have advanced liver disease following specialist review, compared to 3 patients previously identified through standard care (odds ratio [OR] 6.71 [2.0-22.7] p = 0.0022). Alcohol (OR 1.05 [1.02-1.08] p = 0.001) and BMI (OR 1.09 [1.01-1.17] p = 0.021) were predictors of advanced disease, particularly drinking >14/21 units/week (p <0.0001).
UNASSIGNED: Incorporating 2-tier assessment of liver fibrosis into routine annual diabetes review in primary care significantly improves identification of advanced liver disease in patients with T2DM.
UNASSIGNED: People with type 2 diabetes are at increased risk of developing non-alcoholic fatty liver disease and developing more significant complications. This study looks at introducing screening for advanced liver disease into the annual diabetes reviews performed routinely in primary care; we found that significantly more people were identified as having significant liver disease through this pathway than with current standard care.

One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.

Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by persistent pathologic activation of cytotoxic T lymphocytes, natural killer cells, and macrophages. We present details of a young patient who presented with high-grade fever, jaundice, and breathlessness. On investigations, he had hepatitis, anemia, neutropenia, and coagulopathy. He also had hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. Bone marrow aspiration revealed histiocytosis, and transjugular liver biopsy revealed necrotizing granulomas positive for Mycobacterium tuberculosis on acid-fast bacilli staining. He was successfully managed with a combination of immunosuppressants and antitubercular therapy. Tuberculosis associated hemophagocytosis syndrome is rare and should be considered in patients with unexplained hemophagocytosis syndrome, especially in tuberculosis-endemic regions. Prompt recognition and treatment with antitubercular treatment and immunosuppressants are associated with good outcomes.

Ovaries are a common niche for metastasis. Metastatic malignancies account for 5-30% of all ovarian malignancies. Hepatocellular carcinoma (HCC) is one of the rare malignancies to metastasize to the ovaries. Of all the variants of HCC, fibrolamellar HCC (FLHCC) variant is extremely uncommon and accounts for around 1% of all HCC cases. FLHCC metastasizing to ovaries, at presentation, is an exceptional occurrence. We present a case of a young female who presented with bilateral adnexal masses and was diagnosed as metastatic FLHCC on histopathological examination and confirmed by immunohistochemistry. In addition, a thorough literature review highlighting the previously reported cases is also presented.

As part of the United States Pharmacopeia\'s ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities, but no evidence of their involvement in GTE-induced liver injury was found during this review. GTE catechin profiles vary significantly with manufacturing processes. Animal and human data indicate that repeated oral administration of bolus doses of GTE during fasting significantly increases bioavailability of catechins, specifically EGCG, possibly involving saturation of first-pass elimination mechanisms. Toxicological studies show a hepatocellular pattern of liver injury. Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 mg to ∼1000 mg/day and substantial inter-individual variability in susceptibility, possibly due to genetic factors. Based on these findings, USP included a cautionary labeling requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: \"Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes).\"

BACKGROUND: Hepatocellular carcinoma (HCC) in non-cirrhotic livers is an uncommon finding and can present insidiously in patients. Another uncommon finding in HCC, and one of poor prognosis, is the presence of paraneoplastic diseases such as hypercalcemia. We report a case of a 66-year-old previous healthy Filipina woman who after routine laboratory evaluation was discovered to have hypercalcemia as the first sign of an advanced HCC without underlying cirrhosis. Because of the patient\'s relative lack of symptoms, healthy liver function, lack of classical HCC risk factors, and unexpected hypercalcemia, the diagnosis of a paraneoplastic syndrome caused by a noncirrhotic HCC was unanticipated.
METHODS: Case Analysis with Pubmed literature review.
RESULTS: It is unknown how often hypercalcemia is found in association with HCC in a non-cirrhotic liver. However, paraneoplastic manifestations of HCC, particularly hypercalcemia, can be correlated with poor prognosis. For this patient, initial management included attempts to lower calcium levels via zoledronate, which wasn\'t completely effective. Tumor resection was then attempted however the patient expired due to complications from advanced tumor size.
CONCLUSIONS: Hypercalcemia of malignancy can be found in association with non-cirrhotic HCC and should be considered on the differential diagnosis during clinical work-up.