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Background Male osteoporosis is under-diagnosed and poorly studied. With the ageing population, osteoporotic fracture in men is an emerging health problem. The aim of this study was to study the prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in elderly men (>60 years old) attending the outpatient department (OPD). Methods An observational cross-sectional study was performed in elderly men (>60 years old) attending OPD of a tertiary care hospital of Western Maharashtra between April 2017 and June 2019. Patients with rheumatological disorders, history of vertebral/femoral fractures, chronic kidney disease, chronic liver disease, thyroid disorders and alcohol dependence were excluded. Data were analysed using the chi-square test and descriptive statistics. Results In total, 408 male patients were included. The mean age was 68.33 years. Osteoporosis was seen in 39.5% of patients (161/408) with a T score of ≤2.5. Osteopenia was noted in 48.3% of patients (197/408). T and Z scores had significant correlation (p = Conclusion Osteoporosis was noted in 39.5% of the elderly men. In addition, decreased testosterone, COPD and BPH were significantly associated with male osteoporosis. It is important to screen elderly men to diagnose osteoporosis early and prevent osteoporotic fractures.

Hepatopulmonary syndrome (HPS) is a serious complication of chronic liver disease, characterised by portal hypertension and arterial hypoxaemia due to intrapulmonary vascular dilatation. We report an unusual case in which a 27-year-old man had a first presentation of portal hypertension and cirrhosis complicated by HPS. This patient presented with progressive dyspnoea on exertion and deterioration in mobility, with a type 1 respiratory failure and increased oxygen demand. A bubble echocardiogram showed a possible right-to-left shunt, CT aortogram displayed evidence of portal hypertension and cirrhosis, and liver biopsy findings were consistent with alpha-1 antitrypsin deficiency. The patient’s increased oxygen demand was subsequently treated with continuous positive airway pressure before he was discharged with 8 L home oxygen. With no current established medical therapy for HPS, the patient was assessed for liver transplantation and a decision was made in favour of this.

Aim Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7), a transmembrane-anchored endonuclease, is associated with triglycerides level and processing of transferrin receptor 1. However, the significance of circulating PCSK7 has not been fully addressed, though prosegment PCSK7 is secreted from cells. We investigated the associations of plasma PCSK7 level with several parameters. Methods Plasma PCSK7 concentration was measured in 282 subjects (male/female: 126/156) without medication of the Tanno-Sobetsu Study, a population-based cohort study. Results There was no significant sex difference in PCSK7 level. Current smoking habit, but not alcohol drinking habit, was associated with increased PCSK7 level. PCSK7 concentration was negatively correlated with age and blood urea nitrogen and was positively correlated with body mass index (BMI) and levels of γ-glutamyl transpeptidase (γGTP), triglycerides and fatty liver index (FLI), which is calculated by BMI, waist circumference and levels of γGTP and triglycerides, as a noninvasive and simple predictor of NAFLD. There were no significant correlations of PCSK7 level with levels of iron and plasma PCSK9, a secreted PCSK family member and a regulator of low-density lipoprotein cholesterol level. Multivariable regression analyses after adjustment of age, sex and current smoking habit showed that PCSK7 concentration was independently associated with BMI (β=0.130, P=0.035), triglycerides (β=0.141, P=0.027) or FLI (β=0.139, P=0.030). Conclusions Plasma PCSK7 concentration is independently associated with chronic liver disease including obesity and elevated triglycerides level in a general population of individuals who had not regularly taken any medications.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) continues to have a devastating impact across the globe. However, little is known about the disease course in patients with autoimmune hepatitis (AIH). Methods Data for patients with AIH and SARS-CoV-2 infection were combined from three international reporting registries and outcomes were compared to those with chronic liver disease of other aetiology (non-AIH CLD) and to patients without liver disease (non-CLD). Results Between 25th March and 24th October 2020, data were collected for 932 patients with CLD and SARS-CoV-2 infection including 70 with autoimmune hepatitis (AIH). Fifty-eight (83%) of AIH patients were taking one or more immunosuppressive drug. There were no differences in rates of major outcomes between AIH and non-AIH CLD including hospitalization (76% vs 85%; p= 0.06), ICU admission (29% vs. 23%; p=0.240), and death (23% vs. 20%; p=0.643). Factors associated with death within the AIH cohort included age (OR 2.16/10 years; 1.07–3.81), Child-Turcotte-Pugh (CTP) class B (OR 42.48; 4.40–409.53), and CTP-C cirrhosis (OR 69.30; 2.83–1694.50), but not use of immunosuppression. Propensity score matched (PSM) analysis comparing AIH with non-AIH CLD demonstrated no increased risk adverse outcomes including death (+3.2%; -9.2%–15.7%). PSM analysis of AIH versus non-CLD patients (n=769) demonstrated increased risk of hospitalization with AIH (+18.4%; 5.6–31.2%), but equivalent risk of all other outcomes including death (+3.2%; -9.1%–15.6%). Conclusion AIH patients were not at increased risk of adverse outcomes despite immunosuppressive treatment compared to other causes of CLD and to matched cases without liver disease., Graphical abstract, Highlights • This is the largest cohort of patients with autoimmune hepatitis and laboratory proven SARS-COV-2 infection reported to date. • There were no differences in rates of major adverse COVID-19 outcomes including hospitalization, intensive care unit (ICU) admission, and death between AIH patients and those with other aetiologies of liver disease. • When compared to patients without liver disease in propensity score matched analysis, patients with AIH had higher rates of hospitalization but no increased risk of ICU admission or death despite potential reporting of AIH cases with more severe baseline liver disease. • Independent risk factors for death in AIH patients were age and baseline liver disease severity, but not the use of immunosuppression., Lay summary: Little is known about the outcomes of COVID-19 in patients with autoimmune hepatitis (AIH), a rare chronic inflammatory liver disease. This study combines data from three large registries to describe the course of COVID-19 in this patient group. We show that AIH patients do not appear to have an increased risk of death from COVID-19 compared to patients with other forms of liver disease and compared to patients without liver disease, despite the use of medications which suppress the immune system.

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.

We appreciate the interest in our study by Majumdar and Tsochatzis1 and welcome the opportunity to provide some clarifications. The literature to date has examined non-invasive test (NIT) algorithms to rule-in and rule-out advanced fibrosis (AF). The main use of such algorithms is to identify those at low risk of AF who can be managed in primary care. We propose an algorithm2 where the rule-out cut-offs remain optimised for AF, whereas the rule-in cut-offs are optimised for cirrhosis. The false-negative (FN) rate of 10% in our proposed algorithm refers to the FN rate for AF and not cirrhosis as Majumdar and Tsochatzis state in their letter.1 Only 18/570 (3%) of patients with cirrhosis are missed using our proposed algorithm (table 1). View this table: Table 1 Number of patients with fibrosis stage F0–2, F3 and F4 according to LSM cut-offs recommended by the Baveno 6 consensus (10 and 15 kPa) and our previous paper (8 and 20, and 8 and 28 kPa) We also argue2 that patients with NITs above the rule-in cut-off for AF should undergo liver biopsy to identify those with cirrhosis who should undergo …

BACKGROUND AND AIMS: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up. METHODS: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy. RESULTS: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9–35) months. The 1-year and 3-year rate of VB with all NITs was 5.7–7.4% and 13.2–16.4% among high-risk and 0–2.3% and 0–5% among low-risk subgroups, respectively (P

Background Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on outcome of cirrhosis patients in post-hospitalization period are limited. Aims We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results Cirrhosis patients with (n=92) or without (n=92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P=0.520), over a similar duration of follow-up [186 (86-271) vs 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed re-hospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P=0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Background/Aims: Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.Methods: Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.Results: LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.Conclusions: These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Background & aims There is no “gold standard” tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis. Methods 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period. Results 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4–51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4–54.2)], alcohol-related cirrhosis [OR 4.2 (1.1–16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4–2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1–0.4)] scores. Conclusions LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide. Despite the high prevalence, no screening recommendations yet exist. We designed a prospective observational study to estimate the prevalence of NAFLD in the family of patients with NAFLD and develop a predictive model for identifying it. METHODOLOGY: The prevalence of NAFLD in patients’ family members was estimated using ultrasonography, and univariate and multivariate odds were calculated for its predictors. A model was created using the significant parameters on multivariate odds, and its performance was tested using the area under the receiver operating characteristic (AUROC). RESULTS: Among 447 family members of 191 patients with NAFLD, the prevalence of NAFLD was 55.9%. Family members with NAFLD were younger and had lower serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), triglycerides. The liver stiffness measurement and controlled attenuation parameter values were also lesser in family members compared to the index cases. Age, body mass index (BMI), and ALT were independent predictors of NAFLD in the family members. A model combining age and BMI had an AUROC of 0.838 [95% confidence interval (CI) 0.800–0.876, P < 0.001]. Age ≥30 years and BMI ≥25 kg/m(2) had an odds ratio of 33.5 (95% CI 17.0–66.0, P < 0.001) for prediction of NAFLD, in comparison to BMI

BACKGROUND/OBJECTIVES: Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic β-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis. METHODS: A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results. RESULTS: HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P 15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.

BACKGROUND: Sickle cell disease (SCD) is a rare hemoglobinopathy which can result in chronic liver disease and cirrhosis. Patients with SCD have an increased risk of hematologic malignancy, but the prevalence of hepatocellular carcinoma (HCC) in this population is unknown. Herein, the association of SCD with HCC was examined using registry data. METHODS: The SEER-Medicare database was queried to identify patients diagnosed with HCC between 2000 and 2015, and further stratified by SCD status. Propensity matching was performed to examine cancer-related survival and treatment outcomes. RESULTS: Overall 56,934 patients with HCC were identified, including 81 patients with SCD. Patients with SCD more frequently had cirrhosis [48.1% (39/81) vs 23.5% (13,377/56,853), p

Obesity and its associated comorbidities are rapidly increasing in the US population. Therefore, metabolic associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD), has become a leading indication for liver transplantation. Lifestyle modifications as a sole therapy have been insufficient to reduce the burden of chronic liver disease secondary to MAFLD. Endoscopic bariatric interventions (EBI) appear to be safe and effective therapies for obesity and chronic liver disease secondary to MAFLD. Gastric EBI include endoscopic sleeve gastroplasty (ESG) and intragastric balloons (IGB). Small bowel EBI are also evolving in the field of bariatric endoscopy.

Physiologic aging leads to attrition of telomeres and replicative senescence. An acceleration of this process has been hypothesized in the progression of chronic liver disease. We sought to examine the association of telomere length (TL) with liver disease and its impact on mortality risk. A cohort of 7,072 adults with leukocyte TL measurements from the National Health and Nutrition Examination Survey 1999‐2002 with mortality follow‐up through 2015 was analyzed. Liver disease was defined by aminotransferase levels and classified into etiology‐based and advanced fibrosis categories. Multivariable‐adjusted linear regression models estimated effect sizes, with 95% confidence intervals (CIs), of the presence of liver disease on TL. Cox regression models evaluated associations between TL and all‐cause mortality risk using adjusted hazard ratios (HRs). The cohort was representative of the US population with mean age 46.1 years and mean TL 5.79 kilobase pairs. No overall association between TL and liver disease was found; however, there was a significant negative association of TL and advanced liver fibrosis in individuals aged 65 and above. The liver disease cohort (HR 1.22, 95% CI 0.99‐1.51) and those with metabolic syndrome (HR 1.26, 95% CI 0.96‐1.67) had increased mortality risk with shorter TL. The relationship between TL and all‐cause mortality was stronger in women (HR 1.51, 95% CI 1.02‐2.23) and in non‐Hispanic Whites (HR 1.37, 95% CI 1.02‐1.84). Conclusion: Shortened leukocyte TL is independently associated with advanced liver disease at older ages, and with a higher risk of all‐cause mortality in those with liver disease. These associations reaffirm the need to better understand the role of telomeres in the progression of liver disease., We examined the association of peripheral telomere length with liver disease and assessed its impact on mortality using data from the National Health and Nutrition Examination Survey (NHANES). We discovered that shortened leukocyte telomere length is independently associated with advanced liver disease at older ages, and also with a higher risk of all‐cause mortality in those with liver disease.

Background : The purpose of the study was to assess the epidemiology, risk factors and outcomes of native vertebral osteomyelitis (NVO) in patients with Staphylococcus aureus bacteremia (SAB). Methods : A retrospective institutional review was conducted at Mayo Clinic, Minnesota. Patients aged ≥ 18 years with SAB who developed NVO from January 1, 2006 to December 31, 2020 were included and 3-month follow-up data were abstracted. Data pertaining to patient demographics, risk factors and outcomes were recorded using REDCap. A 1:2 nested case-control analysis was performed, and controls were matched according to age, sex and year of SAB diagnosis. Results : A total of 103 patients had NVO. A majority (60.2%) of patients was male, with a median age of 62.0 years. Thirty-one (30.1%) cases were caused by methicillin-resistant S. aureus (MRSA). The lumbar spine was most commonly (57.6%) and the most commonly reported comorbid conditions included diabetes mellitus (36.9%) and coronary artery disease (27.2%). Mortality at three-month follow-up was 18.6%. Nested case-control analysis revealed that injection drug use (IDU) and tobacco consumption were significant risk factors associated with NVO, while chronic hemodialysis and chronic liver disease (CLD) were associated with a decreased risk of NVO. Conclusions : Atherosclerotic vascular disease was prominent in our contemporary cohort with NVO in the setting of SAB. Diabetes mellitus, tobacco consumption, older age and male sex likely contributed to this profile. Because IDU was associated with NVO, an increased number of cases should be anticipated among patients with IDU given the ongoing opioid epidemic in the United States.

Objectives: To identify association of underlying pre-morbidities with disease severity and mortality in hospitalized patients with Corona virus disease 2019. Methods: Total 884 COVID RT-PCR positive patients admitted to KRL Hospital Islamabad from April 2020 to August 2020 were included in this cross-sectional study. Pre-morbidities recorded were hypertension, diabetes mellitus, ischemic heart disease, chronic respiratory disease, chronic kidney disease, chronic liver disease, chronic neuro-psychiatric conditions (stroke and depression) and malignancy. Oxygen requirement, requirement of invasive ventilation, and outcome (recovered versus died) was documented. WHO categories for disease severity were used. Demographic profile and symptoms were also noted. SPSS 22 was used for data analysis. Pearson’s Chi square test was used to see association between pre-morbidities and disease severity categories, oxygen requirement, invasive ventilation and outcome. Pearson’s correlation was applied to analyze the correlation between individual pre-morbidities and disease severity categories. P-value < 0.05 was considered statistically significant. Results: The mean age was 40 ± 12.21 years with 98.5% being males. Majority patients (74.8%) were asymptomatic. Fever was the most common symptom. Diabetes mellitus and hypertension were the most commonly recorded co-morbidity. Significant correlation (p-value < 0.05) was found between the presence of underlying pre-morbidities and disease severity as well as oxygen requirement, requirement of invasive ventilation and mortality. Conclusion: Results are compatible with worldwide studies and underlying pre-morbidities are convincing risk factors for disease severity and mortality. doi: https://doi.org/10.12669/pjms.38.1.4235 How to cite this:Toori KU, Qureshi MA, Chaudhry A. Pre-morbidity and COVID-19 disease outcomes in Pakistani population: A cross-sectional study. Pak J Med Sci. 2022;38(1):287-292. doi: https://doi.org/10.12669/pjms.38.1.4235 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Objectives: To determine the frequency of Non-Alcoholic Fatty Liver Disease (NAFLD) and its associated risk factors among Type-2 Diabetic patients. Methods: This cross-sectional study was conducted in Diabetic Clinic of Shaikh Zayed Postgraduate Medical Institute Lahore from September 2019-February 2020. Type-2 diabetics regardless of age were divided into two groups, one with fatty liver disease and the other without this, evaluated by Abdominal Ultrasonography and were further evaluated by measurement of BMI, obesity, HbA1c and lipid profile. Exclusion criteria were patients having history of or currently taking alcohol, chronic Liver Disease of any cause and intake of hepatotoxic drugs. Qualitative measures were compared between groups by using Chi-square test. Binary logistic regression was used to see the association of factors with fatty liver disease. P-value ≤ 0.05 was considered significant. Results: A total of 185 subjects were included in the study with the mean age of 53.0±9.0 years. About 54.6% patients were diagnosed to have fatty liver disease. When compared the cases with and without fatty liver disease, age and HDL cholesterol had no significant difference between groups while other measures like BMI, TGs & cholesterol levels, ALT and AST were significantly higher among cases with NAFLD. BMI >24.5, HbA1c >7.0 and ALT >40.0 can predict NAFLD among Type-2 diabetic patients with 96.8% accuracy. Conclusion: There is high prevalence of NAFLD among Type-2 diabetic patients and strong association between Type-2 diabetics with NAFLD and risk factors like; obesity, high HbA1c, hyperlipidemia and high ALT. Therefore, early recognition by ultrasonography in high risk patients and intervention like life style modification, maintenance of healthy weight, obesity prevention, treatment of dyslipidemia and good glycemic control should be achieved in such subjects and can prevent NAFLD. doi: https://doi.org/10.12669/pjms.38.1.4968 How to cite this:Ali A, Amin MJ, Ahmed MU, Taj A, Aasim M, Tabrez E. Frequency of non-alcoholic fatty liver disease (NAFLD) and its associated risk factors among Type-2 diabetics. Pak J Med Sci. 2022;38(1):28-33. doi: https://doi.org/10.12669/pjms.38.1.4968 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

To compare initial clinical/laboratory parameters and outcomes of mortality/rebleeding of endoscopy performed12 h(early UGIE) versus endoscopy performed after 12-24h(late UGIE) of ED admission in children with acute upper gastrointestinal bleeding(AUGIB) due to portal hypertension.This is a retrospective cohort study. From January 2010 to July 2017, medical records of all children admitted to a tertiary care hospital with AUGIB due to portal hypertension were reviewed until 60 days after ED admission.A total of 98 ED admissions occurred from 73 patients. Rebleeding was identified in 8/98(8%) episodes, and 9 deaths were observed. UGIE was performed in 92(94%) episodes, and 53(58%) of them occurred within 12 h of ED admission. Episodes with early UGIE and late UGIE were similar in terms of history/complaints/laboratory data at admission, chronic liver disease associated, AUGIB duration, and initial management. No statistically significant associations were found between early UGIE and the outcomes of death/rebleeding and prevalence of endoscopic hemostatic treatment (band ligation or sclerotherapy) compared to late UGIE. In the multivariable logistic regression model, the endoscopic hemostatic treatment showed a negative association with early UGIE(OR=0.33;95%CI=0.1-0.9;p = 0.04).This study suggests that in pediatric patients with AUGIB and portal hypertension, UGIE may be performed after 12-24 h without harm to the patient, facilitating better initial clinical stabilization/treatment and optimization of resources.

Objectives: This study aimed to validate Baveno-VI recommendations for variceal screening in cACLD in our region and proposed our own cutoff values. Methods: Prospective cross-sectional study was conducted on cACLD patients from August 2020 till April 2021. Patients segregated into Group-A, having Liver stiffness measurement (LSM) of ≥ 20 kPa and platelet of ≤ 150 × 109 cells/L; and Group-B having LSM of < 20 kPa and PLT of > 150 × 109 cells/L. Gastroscopic findings were segregated into three categories, VNT, Varices Not Needing Treatment (VNNT) and No Varix (NV). ROC plots were generated for LSM and Platelet for VNT for sensitivity, specificity, Negative and Positive Predictive Values were calculated. Results: A total of 134 patients of cACLD were included. Group-A had 72 (53.7%) patients and Group-B had 62 (46.3%) patients. Group-A had 6 (8.3%) NV; 18 (25.0%) VNNT and 48 (66.7%) VNT. Group-B had 26 (41.9%) NV, 24 (38.7%) VNNT and 12 (19.4%) VNT. The sensitivity of 66.7%, specificity of 80.6% and NPV of 67.56% was obtained. Thus 19.4% VNT were missed on following Baveno VI recommendations. ROC in our study suggested cutoff value of 11.5 kPa with sensitivity of 100% and 1-sepcifity pf 78% (AUROC = 0.865; p < .001) of LSM below which screening gastroscopy could be avoided. The positive and negative predicted values for 84.85% and 100% respectively. Cut off value of platelet count for VNNT came out to be ≥ 97.5 × 109 cells/L with AUROC 0.891 (p < .001), having sensitivity of 100 % and 1-specificity of 83.3%. Conclusions: Substantial number of VNT in cACLD patients are missed by following Baveno-VI recommendations and these needs to be revised on regional basis. List If Abbreviations: AASLD: American Association for Study of Liver Diseases (AASLD), AUROC: Area Under Receiver Operating Characteristic, cACLD: Compensated Advance Chronic Liver Disease (cACLD), CTP: Child-Turcotte-Pugh, DCLD: Decompensated Chronic Liver Disease (DCLD), EV: Esophageal Varices, KPa: Kilo Pascal, LSM: Liver stiffness measurement (LSM), NPV: Negative Predictive Value, NV: No Varix (NV)., PPV: Positive Predictive Value, ROC: Receiver Operating Characteristic, VNNT: Varices Not Needing Treatment (VNNT) and VNT: Varices Needing Treatment (VNT). How to cite this:Ali FS, Bader N, Zuberi BF, Rasheed T. Are we missing varices by implementing Baveno-VI recommendation of not screening patients with Compensated Advanced Chronic Liver Disease? Pak J Med Sci. 2022;38(1):1-8. doi: https://doi.org/10.12669/pjms.38.1.4796 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background Single nucleotide polymorphisms (SNPs) in genes including PNPLA3, TM6SF2, HSD17B13 and SERPINA1 have been identified as risk modifiers of progression in chronic liver disease (CLD). However, it is unclear whether genotyping for these risk variants is useful in clinical routine. Methods Liver disease severity was assessed by liver stiffness measurement (LSM) and by presence of clinical manifestations of advanced-chronic liver disease (ACLD) in 779 consecutive CLD patients at the time of referral to a tertiary center. The associations of risk variants with CLD severity were calculated individually and in a combined model using a polygenic risk-score. Results Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (n = 511, 65.6%), and ACLD was present in 217 (27.9%) patients. The PNPLA3-G-allele remained independently associated with higher LSM (adjusted-B: 2.508 [95%CI: 0.887–4.130], P = 0.002) or the presence of ACLD (aOR: 1.562 [95%CI: 1.097–2.226], P = 0.013). SERPINA1-Z-allele was also independently associated with LSM (adjusted-B: 4.558 [95%CI: 1.182–7.934], P = 0.008), while the other risk alleles did not attain statistical significance. Combining these risk alleles into a polygenic risk-score was significantly associated with LSM (adjusted-B: 0.948 [95%CI: 0.153–1.743], P = 0.020). Conclusion PNPLA3 risk-variants are linked to liver disease severity at the time of first referral to an outpatient hepatology clinic.

Objectives Liver transplantation is used to treat both patients with end-stage liver diseases and those with hepatocellular carcinoma; in Iran, these patients are commonly infected with hepatitis B and C viruses. In the present study, for the first time, we investigated the association between ACOX1 and NRF1 gene and protein expression and presence of hepatitis B virus, hepatitis C virus, and hepatocellular carcinoma in liver transplant patients in South-Central Iran. Materials and methods In this cross-sectional study, we included 200 patients who were seen between 2008 and 2017 for liver transplant at the Namazi Hospital, Shiraz University of Medical Sciences (Shiraz, Iran). All patients received liver grafts from brain dead donors. Donors and recipients were unrelated. ABO compatibility blood group analyses for donor-recipient pairs were conducted. Liver transplant recipients were divided into 3 different groups: hepatitis B virus infected, hepatitis C virus infected, and presence of hepatocellular carcinoma. We also had a control group that included 30 healthy individuals. NRF1 and ACOX1 gene expression levels were evaluated using the SYBER green real-time polymerase chain reaction method. NRF1 and ACOX1 protein expression levels were evaluated using enzymelinked immunosorbent analyses. We used SPSS software for statistical analyses (version 19.0). Results NRF1 gene expression was increased in all 3 liver transplant recipient groups compared with the control group (not significant, P > .05). Furthermore, ACOX1 gene expression was decreased in all patients compared with control (P > .05). However, we found ACOX1 and NRF1 protein expression to be significantly decreased in all 3 liver transplant recipients groups compared with the control group (P Conclusions NRF1 and ACOX1 genes and their protein expressions could affect the development of chronic liver disease.

Background: Gut microbial alterations have been linked to chronic liver disease and hepatocellular carcinoma (HCC). The role of the oral microbiome in liver cancer development has not been widely investigated. Methods: Bacterial 16S rRNA sequences were evaluated in oral samples from 90 HCC cases and 90 controls who were a part of a larger U.S. case–control study of HCC among patients diagnosed from 2011 to 2016. Results: The oral microbiome of HCC cases showed significantly reduced alpha diversity compared with controls (Shannon P = 0.002; Simpson P = 0.049), and beta diversity significantly differed (weighted Unifrac P = 0.004). The relative abundance of 30 taxa significantly varied including Cyanobacteria, which was enriched in cases compared with controls (P = 0.018). Cyanobacteria was positively associated with HCC [OR, 8.71; 95% confidence interval (CI), 1.22–62.00; P = 0.031] after adjustment for age, race, birthplace, education, smoking, alcohol, obesity, type 2 diabetes, Hepatitis C virus (HCV), Hepatitis B virus (HBV), fatty liver disease, aspirin use, other NSAID use, laboratory batch, and other significant taxa. When stratified by HCC risk factors, significant associations of Cyanobacteria with HCC were exclusively observed among individuals with negative histories of established risk factors as well as females and college graduates. Cyanobacterial genes positively associated with HCC were specific to taxa producing microcystin, the hepatotoxic tumor promotor, and other genes known to be upregulated with microcystin exposure. Conclusions: Our study provides novel evidence that oral Cyanobacteria may be an independent risk factor for HCC. Impact: These findings support future studies to further examine the causal relationship between oral Cyanobacteria and HCC risk.

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients.Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals.Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57).Conclusions: We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.

© 2023 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., Background & aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines., Partial funds were provided through Fundação para a Ciência e a Tecnologia (grants PTDC/MED-PAT/31882/2017 and EXPL/MED-OUT/1317/2021) and through La Caixa Scientific Foundation (grant HR17-00601).

The impact of alcoholic hepatitis (AH) on health-related quality of life (HRQOL) remains inadequately described. We aimed to characterize HRQOL in AH and heavy drinkers (HD), and its associations with clinical variables and outcomes.This is a post hoc analysis of participants in the Translational Research and Evolving Alcoholic Hepatitis Treatment 001 study (NCT02172898). HRQOL was measured using Short Form Health Survey (SF-36). Mean SF-36 scores were compared in AH and HD with two-sample t-tests. Associations among clinical characteristics, 30-day mortality, and SF-36 mental and physical component scores (MC, PC) were investigated with generalized linear and logistic multivariate regression models. Trends of MC and PC scores were analyzed using one-way ANOVA.Participants with AH (n = 258) and HD (n = 181) were similar demographically. AH cases had a mean Model for End-stage Liver Disease (MELD) score of 23 (7). AH cases had lower PC scores [37 (10) vs. 48 (11), p 0.001] but higher MC scores [37 (13) vs. 32 (13), p 0.001]. MC scores were independently associated with age, male gender, and daily alcohol consumption; PC scores were independently associated with age, BMI, alanine aminotransferase concentration, alkaline phosphatase concentration, white blood cell counts, and the presence of ascites. With each 5-point decrease in the baseline PC score, the adjusted odds of dying within 30 days increased by 26.7% (95% CI 1% to 46%). Over time, HRQOL in AH improved (day 0 to day 180 delta PC score: 4.5 ± 1.7, p = 0.008; delta MC score: 9.8 ± 2.0, p 0.001). Participants with a MELD score15 by day 180 had greater increases in PC scores than those with MELD score ≥15 (delta PC score 7.1 ± 1.8 vs. -0.7 ± 2.3, p = 0.009), while those abstinent by day 180 had greater increases in MC scores than those who were not abstinent (delta MC score 9.1 ± 1.8 vs. 2.8 ± 2.4, p = 0.044).HRQOL is poor in AH and HD in a domain-specific pattern. Independent of MELD score, lower baseline HRQOL is associated with higher 30-day mortality. Over time, HRQOL improves with greater gains seen in individuals with improved MELD scores and those who were abstinent.

OBJECTIVES The relevance of candidemia has increased over the last decades due to higher incidence rates in an aging society. Studies on amphotericin B and fluconazole have shown high attributable mortality rates of 38% and 49% in the US. Incidence rates and locational factors might have an impact on the mortality rates at the University Hospital of Cologne (UHC), Germany. METHODS We performed a matched case-control study including 57 patients with candidemia, hospitalized at the UHC between 1st of July 1997 and 30th of June 2001. Controls were matched by age, sex, admission date, treatment on intensive care unit (ICU), number of days at risk, underlying diseases, surgical procedures, and the Charlson Comorbidity Index. RESULTS The incidence of candidemia was 3.5 per 10,000 admissions. For cases and controls, we observed in-hospital-mortality rates of 33.3% and 11.8%, and a 30-day mortality of 23.5% and 7.8%, respectively. The attributable mortality rate to candidemia was 21.5%, and at 30-days it was 15.7%. Underlying conditions were more frequent in cases than in controls, especially central venous catheter (80% vs. 33% p

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease globally. miRNAs (miRs) regulate various cellular events that lead to NAFLD. In this study we tested the hypothesis that miR-155 is an important regulator of steatohepatitis and fibrosis pathways. Wild type (WT) or miR-155 deficient (KO) mice received a high fat-high cholesterol-high sugar-diet (HF-HC-HS) for 34 weeks and liver tissues were analyzed. In patients with nonalcoholic steatohepatitis and in the mouse model of HF-HC-HS diet we found increased miR-155 levels in the liver compared to normal livers. Upon HF-HC-HS diet feeding, miR-155 KO mice displayed less liver injury, decreased steatosis, and attenuation in fibrosis compared to WT mice. ALT, triglyceride levels, and genes involved in fatty acid metabolic pathway were increased in WT mice whereas miR-155 KO mice showed attenuation in these parameters. HF-HC-HS diet-induced significant increase in the expression of NLRP3 inflammasome components in the livers of WT mice compared to chow fed diet. Compared to WT mice, miR-155 KO showed attenuated induction in the NLRP3, ASC, and caspase1 inflammasome expression on HF-HC-HS diet. Fibrosis markers such as collagen content and deposition, αSMA, Zeb2, and vimentin were all increased in WT mice and miR-155 KO mice showed attenuated fibrosis marker expression. Overall, our findings highlight a role for miR-155 in HF-HC-HS diet-induced steatosis and liver fibrosis.

Background &Aims Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials of vaccine studies against SARS-CoV-2. Although clinical efficacy of COVID vaccines in immunocompromised patients was unknown, many societies had recommended vaccination of this highly vulnerable patient population. Methods In this prospective study, we determined antibody (Ab) response to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis. Results Of the 233 patients enrolled so far, 62 had LT, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Ab titers were defined as undetectable (250 U/mL). Of the 62 patients who had LT, Ab levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47 - 212 U/mL) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable Ab and 15 had suboptimal (median titer 41.3, range 0.49 - 221 U/L) response. Of the 92 patients without cirrhosis, four had undetectable Ab and 19 had suboptimal (median titer 95.5, range 4.9 - 234 U/L) Ab response. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. Conclusions Poor antibody response after SARS-CoV-2 vaccination was seen in 61% of LT recipients and 24% of those with CLD. Lay summary The clinical efficacy of COVID vaccines in immunocompromised patients is unknown. We did a prospective study to evaluate immune responses to COVID vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 subjects with cirrhosis and 92 subjects with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody response (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody response when adjusted for other factors., Graphical abstract

By inhibiting the growth of pathogenic bacteria and modulating the local intestinal immune system, probiotics may reduce bacterial translocation and systemic endotoxaemia, factors partially responsible for post-operative complications following liver resection for hepatocellular carcinoma in patients with cirrhosis. Patients with resectable hepatocellular carcinoma developed in the setting of chronic liver disease were prospectively divided into two equal-sized groups: one receiving probiotic treatment 14 days prior to surgery and the other receiving placebo. The primary endpoint was the level of circulating endotoxins after hepatectomy. Secondary endpoints were systemic inflammation (inflammatory cytokine levels), post-operative liver function and overall post-operative complication rate. From May 2013 to December 2018, 64 patients were randomized, and 54 patients were included in the analysis, 27 in each arm. No significant change in endotoxin levels was observed over time in either group (P = 0.299). No difference between the groups in terms of post-operative liver function and overall complication rates was observed. The only differences observed were significant increases in the levels of TNFalpha (P = 0.019) and interleukin 1-b (P = 0.028) in the probiotic group in the post-operative period. Contrary to the modest data reported in the literature, the administration of probiotics before minor liver resection for hepatocellular carcinoma developed in the setting of compensated chronic liver disease does not seem to have an impact on circulating endotoxin levels or post-operative complication rates. Trial registration: NCT02021253.

AIM The global burden of chronic liver disease is substantial. Limited studies have reported the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis among middle-aged and older people. Therefore, we aimed to determine the nationwide prevalence of and associated factors for MAFLD and fibrosis in adults aged 45-79 years from the United States. METHODS This cross-sectional study utilized data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey conducted with a nationally representative sample of the civilian, noninstitutionalized US population. Hepatic steatosis and fibrosis were assessed by transient elastography with controlled attenuation parameter and liver stiffness measurement, respectively. RESULTS A total of 1186 eligible participants aged 45-79 years were finally included in the analyses. The estimated prevalence of MAFLD, significant fibrosis (F ≥ F2), and advanced fibrosis (F ≥ F3) was 48.6% (95% confidence interval [CI], 43.1%-54.0%), 9.5% (95% CI, 6.8%-12.7%), and 6.7% (95% CI, 4.1%-10.1%), respectively. Multivariable logistic regression revealed an increased MAFLD predisposition in subjects with metabolic disorders including overweight/obesity, abdominal obesity, hypertension, and diabetes mellitus. Moreover, the presence of depression was an independent and strong predictor of MAFLD risk (odds ratio = 3.23; 95% CI, 1.37-7.11). Elevated liver enzymes, hypertension, diabetes mellitus, hepatitis virus infection, and steatosis were associated with a high risk of significant fibrosis. CONCLUSIONS Newly defined MAFLD is highly prevalent in the US middle-aged and older population. Approximately 1 in 10 people has significant liver fibrosis. In addition to metabolic disorders, the presence of depression potentially increases the risk of MAFLD.

OBJECTIVE Hepatocellular carcinoma (HCC) is the sixth among the most common cancers and the fourth among cancer-related causes of death in the world. In the evaluation of liver function in HCC patients, parameters such as albumin-bilirubin, prothrombin time-international normalized ratio (PT-INR) to albumin ratio (PTAR) are used among new methods other than Child-Pugh and MELD scores. Biomarkers are widely used in clinical practice in cases such as diagnosing various diseases, evaluating treatment response and predicting prognosis. We aimed to evaluate the prognostic role of serum ferritin and INR/albumin ratio in patients with chronic liver disease who develop HCC. METHODS This retrospective study included 534 patients who were followed up with the diagnosis of HCC between 2009 and 2020. The patients with HCC etiology were evaluated in 3 groups (chronic hepatitis B group, chronic hepatitis C group, and other group). When comparing serum ferritin level and prothromin time-international normalized ratio to albumin ratio with Child Pugh score (CTP) in chronic liver patients with HCC, liver functional reserve and its role in predicting prognosis were investigated. RESULTS The serum ferritin level was 226 ± 334 in the CTP A group, 239 ± 302 in the CTP B group, and 678 ± 966 in the CTP C group, and the p value was 0.001. The PTAR CTP group was 0.35 ± 0.10, the CTP B group was 0.50 ± 0.26, the CTP C group was 1.18 ± 6.01, and the p value was 0.001. Multivariant analysis results showed that ferritin hazard ratio is 1.00, 95% CI 0.99-1.00, and p value was 0.09, and PTAR hazard ratio is 1.38, 95% CI 2.37-8.00, and p value was 0.49. The etiological distribution of HCC was determined as HBV (61.6%), HCV (19.9%), and other etiologies (18.5%). Significant values were determined for age, gender, glucose, GGT, T. cholesterol, and tumor diameter parameters according to etiological distribution. CONCLUSIONS Serum ferritin level and PTAR score increased in proportion to the severity of liver disease and were associated with poor prognosis. We think that high serum ferritin and PTAR score is a prognostic biomarker in predicting the synthesis function of the liver and mortality in critically ill patients with cirrhosis.

Background: Male breast cancer is a rare disease compared to female breast cancer. The reason of the low incidence rate in men is the relatively low amount of breast tissue along with the difference in their hormonal environment. Even though breast tissue is less in men as compared to women, the factors that influence malignant changes are similar. The rare nature of disease and lack of surveillance system for male breast cancer it makes a difficult disease to study. Present study was carried out to understand clinipathological features of male breast lesions. Materials and Methods: A retrospective descriptive study was carried out in a tertiary care center for 5yeras duration (Jan 2014 to Dec 2018) at pathology department. Demographic, history and histopathological details of male breast lesion were retrieved from database at pathology department. Results: Median age of cases was 58.34+6.67yrs and range of 54-80years. Very few had family history of breast cancer. Alcoholism, obesity and chronic liver disease were risk factors. Most of them were diagnosed as gynecomastia on histopathology findings. One case of phylloid tumor. Conclusion: Changing lifestyle and environmental condition may rise MBC in the future, understanding epidemiology and pathology is need of time for early diagnosis and management. Keywords: Breast, Lesion, Male, Pathology, Risk

BACKGROUND Coronavirus disease 2019 (COVID-19) infection is known to cause abnormal hepatic enzymes. The long term consequences of such elevations are uncertain. AIM To assessed the prevalence and prognostic value of initial liver enzymes in a large cohort of COVID-19 patients. METHODS We reviewed electronic medical records of 10614 COVID-19 patients without known chronic liver disease who were admitted to our health system from March 1, 2020, to April 30, 2020. We analyzed baseline demographics and liver chemistries. The primary outcome was in-hospital mortality, and the secondary outcome was a composite of in-hospital mortality or need for mechanical ventilation. RESULTS Subjects with abnormal liver tests had increased risks of mortality and composite outcome when compared to patients with normal measurements on unadjusted analysis and after adjustment for demographic factors. CONCLUSION In our diverse patient population, liver enzyme abnormalities are associated with increased mortality and the need for mechanical ventilation in subjects without chronic liver disease. Cholestasis patients are at the greatest risk for poor outcomes.

Many safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations dramatically reduce risks of coronavirus disease 2019 (COVID-19) complications and deaths. We aimed to describe cases of SARS-CoV-2 infection among patients with chronic liver disease (CLD) and liver transplant (LT) recipients with at least one prior COVID-19 vaccine dose. The SECURE-Liver and COVID-Hep international reporting registries were used to identify laboratory-confirmed COVID-19 in CLD and LT patients who received a COVID-19 vaccination. Of the 342 cases of lab-confirmed SARS-CoV-2 infections in the era after vaccine licensing, 40 patients (21 with CLD and 19 with LT) had at least one prior COVID-19 vaccination, including 12 who were fully vaccinated (���2 weeks after second dose). Of the 21 patients with CLD (90% with cirrhosis), 7 (33%) were hospitalized, 1 (5%) was admitted to the intensive care unit (ICU), and 0 died. In the LT cohort (n = 19), there were 6 hospitalizations (32%), including 3 (16%) resulting in mechanical ventilation and 2 (11%) resulting in death. All three cases of severe COVID-19 occurred in patients who had a single vaccine dose within the last 1-2 weeks. In contemporary patients with CLD, rates of symptomatic infection, hospitalization, ICU admission, invasive ventilation, and death were numerically higher in unvaccinated individuals. Conclusion: This case series demonstrates the potential for COVID-19 infections among patients with CLD and LT recipients who had received the COVID-19 vaccination. Vaccination against SARS-CoV-2 appears to result in favorable outcomes as attested by the absence of mechanical ventilation, ICU, or death among fully vaccinated patients.