A perspective on varied fungal virulence factors causing infection in host plants.

Pathogenic fungi and their spores are ubiquitously present and invade the tissues of higher living plants causing pathogenesis and inevitably death or retarded growth. A group of fungi kills its hosts and consume the dead tissues (necrotrophs), while others feed on living tissue (biotrophs) or combination of two (hemibiotrophs). A number of virulent factors is used by fungal pathogens to inhabit new hosts and cause illness. Fungal pathogens develop specialized structures for complete invasion into plant organs to regulate pathogenic growth. Virulence factors like effectors, mycotoxins, cell wall degrading enzymes and organic acids have varied roles depending on the infection strategy and assist the pathogens to possess control on living tissues of the plants. Infection strategies employed by fungi generally masks the plant defense mechanism, however necrotrophs are best known to harm plant tissues with their poisonous secretion. Interestingly, the effector chemicals released by Biotrophs reduce plant cell growth and regulate plant metabolism in their advantage causing no direct death. All these virulence tools cause huge loss to the agricultural product of pre- harvest crops and post-harvest yields causing low output leading to huge economic losses. This review focusses on comprehensive study of range of virulence factors of the pathogenic fungi responsible for their invasion inside the healthy tissues of plants. The compiled information would influence researchers to design antidote against all virulence factors of fungi relevant to their area of research which could pave way for protection against plant pathogenesis.

Visceral adiposity in cirrhosis: Association with disease severity and impact of liver transplantation.

BACKGROUND: Changes in adipose tissue distribution in liver cirrhosis are poorly characterized and may affect clinical outcomes. METHODS: Adult liver transplant (LT) January 2008-August 2017 recipients with abdominal MRI within 6 months pre-LT were retrospectively assessed. Visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle area (cm2) were determined at L3. Visceral-to-subcutaneous adipose tissue ratio (VSR) was used to define relative adipose distribution, stratified by sex. Correlation was tested with Pearson. Body composition measures were compared by Child-Turcotte-Pugh (CTP) class, before and after LT, and evaluated as predictors of clinical outcomes. RESULTS: A total of 318 patients were studied. Mean age was 56 years, 33.64% were female, and 47.80% had CTP C cirrhosis. CTP C was associated with a 0.42-point increase in VSR compared with CTP A (95% CI = 0.13-0.71, p < 0.01), adjusting for age, sex, diabetes, and HCC. Among the 79 (24.84%) patients with repeat MRI 1-2 years after LT, VSR significantly improved from before LT (1.31 vs. 0.95, p < 0.01). In adjusted analysis, CTP C was associated with a 0.86-point decrease in post-LT VSR compared with pre-LT VSR (95% CI = -1.27 to -0.44, p < 0.01). Body mass index poorly correlated with VSR before and after LT. Elevated pre-LT VSR trended toward an association with a 7.17-point decrease in pre-LT glomerular filtration rate (95% CI = -14.35 to -0.02, p = 0.05), adjusting for CTP C, age, sex, diabetes, hypertension, pre-LT sarcopenia, and hepatocellular carcinoma. Elevated pre-LT VSR did not affect 3-year post-LT mortality (log-rank p = 0.24). CONCLUSIONS: Poorly represented by body mass index, visceral adiposity is increased in cirrhosis and is associated with CTP class. However, this adipose redistribution may be modifiable by LT.

Statins Are Associated With a Decreased Risk of Severe Liver Disease in Individuals With Noncirrhotic Chronic Liver Disease.

BACKGROUND & AIMS: Little is known about the potential impact of statins on the progression of noncirrhotic chronic liver diseases (CLDs) to severe liver disease. METHODS: Using liver histopathology data in a nationwide Swedish cohort, we identified 3862 noncirrhotic individuals with CLD and statin exposure, defined as a statin prescription filled for 30 or more cumulative defined daily doses. Statin users were matched to 3862 (statin) nonusers with CLD through direct 1:1 matching followed by propensity score matching. Cox regression was used to estimate hazard ratios (HRs) for the primary outcome of incident severe liver disease (a composite of cirrhosis, hepatocellular carcinoma, and liver transplantation/liver-related mortality). RESULTS: A total of 45.3% of CLD patients had nonalcoholic fatty liver disease, 21.9% had alcohol-related liver disease, 17.7% had viral hepatitis, and 15.1% had autoimmune hepatitis. During follow-up evaluation, 234 (6.1%) statin users vs 276 (7.1%) nonusers developed severe liver disease. Statin use was associated with a decreased risk of developing severe liver disease (HR, 0.60; 95% CI, 0.48-0.74). Statistically significantly lower rates of severe liver disease were seen in alcohol-related liver disease (HR, 0.30; 95% CI, 0.19-0.49) and in nonalcoholic fatty liver disease (HR, 0.68; 95% CI, 0.45-1.00), but not in viral hepatitis (HR, 0.76; 95% CI, 0.51-1.14) or autoimmune hepatitis (HR, 0.88; 95% CI, 0.48-1.58). Statin use had a protective association in both prefibrosis and fibrosis stages at diagnosis. Statin use was associated with lower rates of progression to cirrhosis (HR, 0.62; 95% CI, 0.49-0.78), hepatocellular carcinoma (HR, 0.44; 95% CI, 0.27-0.71), and liver-related mortality (HR, 0.55; 95% CI, 0.36-0.82). CONCLUSIONS: Among individuals with noncirrhotic CLD, incident statin use was linked to lower rates of severe liver disease, suggesting a potential disease-modifying role.

Dealkenylation of neoandrographolide, a phytochemical from Andrographis paniculata stimulates FXR (Farnesoid X Receptor) and enhances gallstone dissolution.

FXR (Farnesoid X Receptor) is one of the nuclear receptors expressed in the liver performing a significant role in the maintenance of bile acid concentration. An imbalance of cholesterol and bile acid ratio due to any undefined reason could cause gallstone formation. Hence, this paper aims to screen phytochemicals that could maintain a requisite balance of cholesterol and bile acid by targeting FXR and thereby contributing to the dissolution of gallstone. Nineteen phytochemicals were selected and queried for Pa and Pi in the way2drug online server for hepatoprotective property, cholesterol synthesis and absorption inhibition property, and ß-glucuronidase inhibiting activity. Cianidanol, neoandrographolide, cynarine, saponins, and tanins with satisfying stated properties were docked with the screened FXR (PDB ID- 1OSH) using HADDOCK server, followed by pharmacokinetics study utilizing SwissADME tool. Neoandrographolide fits best among the other selected literature-based phytochemicals with minor violation of 'Brenk's rule'. The violation was corrected with the removal of an alkene group in the provided ChemDraw space of SwissADME. This Dealkenylated compound was further docked with FXR. The promising response under the static condition of the Dealkenylated compound was analyzed for molecular dynamic simulation at physiological conditions for 100 ns. Dealkenylated Neoandrographolide (DN) exhibited hepatoprotective, cholesterol synthesis and absorption inhibition property, and ß-glucuronidase inhibition activity with a superior binding score of -42.6+/-1.5 with FXR. The interaction of the FXR receptor and the DN showed exceptional stability at physiological conditions during MD simulation and fit for the ADME properties, therefore it could be a potent candidate to dissolve gallstones.Communicated by Ramaswamy H. Sarma.

Pregnancy Outcomes in Women With Autoimmune Hepatitis - A Nationwide Population-based Cohort Study With Histopathology.

BACKGROUND & AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver condition that predominantly affects women. However, pregnancy risks remain unclear. METHODS: A nationwide population-based cohort study (ESPRESSO) in Sweden from 1992 to 2016 including 309 singleton births in women with AIH and 1532 matched births in women from the general population was performed. AIH was diagnosed as a combination of administrative coding from medical diagnosis of AIH and liver biopsy data from Sweden's 28 pathology departments. Using conditional logistic regression, odds ratios (ORs) for adverse pregnancy outcomes were determined. RESULTS: Among 306 live births to women with AIH, 51 (16.7%) were preterm, compared with 70 of 1524 (4.6%) reference births. This corresponded to an OR of 5.10 for preterm birth (95% confidence interval [CI], 3.29-7.92), with similar odds using sibling comparators. Women with AIH with and without cirrhosis had similar odds for preterm birth. The AIH association was particularly strong with medically indicated preterm birth (OR, 13.01; 95% CI, 5.50-30.79). AIH was associated with low birth weight (OR, 5.31; 95% CI, 2.82-9.99) and low 5-minute Apgar score (OR, 3.46; 95% CI, 1.14-10.49) offspring, but we found no association with congenital malformations (OR, 1.14; 95% CI, 0.68-1.91), small for gestational age (OR, 1.04; 95% CI, 0.38-2.85), stillbirth (OR, 0.59; 95% CI, 0.02-18.88), or neonatal death (OR, 7.42; 95% CI, 0.65-84.25). Maternal AIH was linked to an increased odds of cesarean section (OR, 1.44; 95% CI, 1.04-2.00) and preeclampsia (OR, 3.65; 95% CI, 2.01-6.64), but not to gestational diabetes. CONCLUSIONS: Maternal AIH was associated with a 5-fold higher odds of preterm birth, and cirrhosis at diagnosis did not add to the impact of AIH on preterm birth. Future studies are needed to understand how to reduce this risk.

Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease.

BACKGROUND & AIMS: Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups. METHODS: We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019. RESULTS: At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis). CONCLUSIONS: Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.

A complete clinico-epidemiological and microbiological profile of candidemia cases in a tertiary-care hospital in Western India.

Objective: To identify different Candida spp along with antifungal susceptibility pattern and risk factors associated with candidemia. Design setting and patients: This retrospective observational study was conducted in a tertiary-care academic hospital in Jaipur, Western India, for 3 years (July 2017-June 2020). Methods: Blood cultures were performed according to standard microbiological methods, and only 1 isolate per patient was included in the study. Isolates of Candida spp were identified using a VITEK-2 automated system and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antifungal susceptibility tests were performed using the broth microdilution assay according to the Clinical and Laboratory Standards Institute guidelines. Results: Of 3,443 blood cultures received from suspected sepsis cases, candidemia was identified in 95 (2.8%). In addition to Candida tropicalis (n = 36; 38%) and Candida parapsilosis (n = 17; 18%), 10 isolates of Candida auris comprised the fourth most common cause of candidemia. Presence of central venous catheter and diabetes were statistically significant risk factors for development of candidemia by NAC. Resistance to fluconazole was 36%, resistance to voriconazole was 20%, resistance to 5-flucytosine was 4%, and resistance to amphotericin-B was 7%. C. auris isolates were more resistant than other NAC spp. We detected no resistance among the echinocandins. Conclusions: The emergence of highly resistant isolates like C. auris emphasizes the need for constant monitoring of candidemia cases for species identification and routine antifungal susceptibility so that appropriate measures can be taken to reduce the related morbidity and mortality.

N-glycosylation, a leading role in viral infection and immunity development.

N-linked protein glycosylation is an essential co-and posttranslational protein modification that occurs in all three domains of life; the assembly of N-glycans follows a complex sequence of events spanning the (Endoplasmic Reticulum) ER and the Golgi apparatus. It has a significant impact on both physicochemical properties and biological functions. It plays a significant role in protein folding and quality control, glycoprotein interaction, signal transduction, viral attachment, and immune response to infection. Glycoengineering of protein employed for improving protein properties and plays a vital role in the production of recombinant glycoproteins and struggles to humanize recombinant therapeutic proteins. It considers an alternative platform for biopharmaceuticals production. Many immune proteins and antibodies are glycosylated. Pathogen's glycoproteins play vital roles during the infection cycle and their expression of specific oligosaccharides via the N-glycosylation pathway to evade detection by the host immune system. This review focuses on the aspects of N-glycosylation processing, glycoengineering approaches, their role in viral attachment, and immune responses to infection.

Risk of infections and their role on subsequent mortality in biopsy-proven alcohol-related liver disease.

BACKGROUND AND AIMS: The risk for infection in alcohol-related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital-based infections in a nationwide cohort of biopsy-proven ALD, and the subsequent risk of death. METHODS: Population-based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals. RESULTS: Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person-years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85-3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36-3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89-4.78) were linked to subsequent death. CONCLUSIONS: Individuals with biopsy-proven ALD have a three-fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.

Risk of Cancer in Biopsy-Proven Alcohol-Related Liver Disease: A Population-Based Cohort Study of 3410 Persons.

BACKGROUND & AIMS: Persons with alcohol-related liver disease (ALD) are at an increased risk of death and liver-related endpoints, but the association with incident cancer is not well understood, and whether it differs across histopathological subgroups is undefined. METHODS: We investigated the risk of cancer in 3,410 persons with a diagnosis of ALD and an available liver biopsy in Sweden between 1969-2016, compared to a matched reference population. Administrative coding from national registers and liver biopsy data were used to define exposure and outcome status. Competing risk regression, adjusted for available confounders and using non-cancer mortality as the competing risk, was used to estimate subdistribution hazard ratios (sHRs) for incident cancer. RESULTS: At baseline, persons with ALD had a median age of 58.2 years, 67% were men, and 2,042 (60%) had cirrhosis. ALD was not associated with cancer in general (sHR = 1.01, 95%CI = 0.92-1.11), although the risk was increased in persons surviving ≥1 year (sHR = 1.19, 95% CI = 1.08-1.32). The risk of liver cancer was elevated sHR = 12.80, 95%CI = 9.38-17.45). HCC incidence among ALD persons with cirrhosis was 8.6 cases/1,000 person-years, corresponding to a cumulative incidence after 10 years of 5.0%. CONCLUSIONS: Persons with biopsy-proven ALD that survive the initial time after diagnosis are at an elevated risk for cancer, in particular HCC compared with the general population. Although the risk for HCC was elevated, data do not suggest that routine surveillance for HCC in ALD cirrhosis is cost-effective.

Cancer Risk in Patients With Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study With Histopathology.

We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969-2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR) = 2.69) and lymphoma (HR = 1.89). Sibling analyses yielded similar risk estimates for any cancer (HR = 1.84) and HCC (HR = 23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.

Risk of severe COVID-19 and mortality in patients with established chronic liver disease: a nationwide matched cohort study.

BACKGROUND AND AIMS: Some, but not all, prior studies have suggested that patients with chronic liver disease are at increased risk of contracting COVID-19 and developing more severe disease. However, nationwide data are lacking from well-phenotyped cohorts with liver histology and comparisons to matched general population controls. METHODS: We conducted a nationwide cohort study of all Swedish adults with chronic liver disease (CLD) confirmed by liver biopsy between 1966 and 2017 (n = 42,320), who were alive on February 1, 2020. CLD cases were matched to ≤ 5 population comparators by age, sex, calendar year and county (n = 182,147). Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 hospitalization and severe COVID-19 (intensive care admission or death due to COVID-19). RESULTS: Between February 1 and July 31, 2020, 161 (0.38%) CLD patients and 435 (0.24%) general population controls were hospitalized with COVID-19 (aHR = 1.36, 95% CI = 1.11-1.66), while 65 (0.15%) CLD patients and 191 (0.10%) controls developed severe COVID-19 (aHR = 1.08, 95% CI = 0.79-1.48). Results were similar in patients with CLD due to alcohol use, nonalcoholic fatty liver disease, viral hepatitis, autoimmune hepatitis, and other etiologies. Among patients with cirrhosis (n = 2549), the aHRs for COVID-19 hospitalization and for severe COVID-19 were 1.08 (95% CI 0.48-2.40) and 1.23 (95% CI = 0.37-4.04), respectively, compared to controls. Moreover, among all patients diagnosed with COVID-19, the presence of underlying CLD was not associated with increased mortality (aHR = 0.85, 95% CI = 0.61-1.19). CONCLUSIONS: In this nationwide cohort, patients with CLD had a higher risk of hospitalization for COVID-19 compared to the general population, but they did not have an increased risk of developing severe COVID-19.

High prevalence of celiac disease in autoimmune hepatitis: Systematic review and meta-analysis.

BACKGROUND: Previous studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore aimed to examine the prevalence of CD in individuals with AIH. METHODS: Two professional librarians searched PubMed, EMBASE, Cochrane and Web of Science Core Collection up until 7 February 2020. The search terms included 'celiac disease', 'celiac', 'transglutaminases', 'gluten', 'gliadin', 'EMA', 'TTG' and 'villous' combined with 'autoimmune', 'hepatitis', 'ANA', 'SMA' and 'LKM'. This search yielded 2419 unique publications. A systematic review based on the PRISMA guidelines resulted in 31 articles eligible for full text review. Fifteen articles were deemed relevant, with 8 being included in our main analysis. A fixed-effect inverse variance-weighted model was used, and heterogeneity was calculated. RESULTS: Our main analysis included 567 individuals with AIH from eight studies, where biopsy-verified CD (equivalent to Marsh III) was seen in 23 individuals (4.1%). The pooled prevalence of CD in AIH was 3.5% (95% CI = 1.6%-5.3%) (heterogeneity: P = .874; I2  = 0.0%), which is clearly higher than the 1% CD seen in most general populations. When also including studies where CD had been diagnosed through positive serology without biopsy (15 studies: n = 1817 individuals with AIH), the pooled prevalence of CD was 2.9% (95% CI = 2.1%-3.8%) (heterogeneity: P < .001; I2  = 66.8%). CONCLUSION: Our results demonstrate a higher prevalence of CD in individuals with AIH compared to the general population. CD screening may be considered in patients with AIH.

Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study.

BACKGROUND AND AIMS: Recent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity. APPROACH AND RESULTS: We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to ≤5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person-years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18-1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; Ptrend  < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers. CONCLUSIONS: Compared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.

Increased Mortality Risk in Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study With Histopathology.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting. METHODS: This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death. RESULTS: During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI = 31.1-33.6) for AIH individuals and 14.1% (95%CI = 13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI = 2.17-2.41), which remained elevated ≥20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR = 4.55; 95%CI = 3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR = 1.27; 95%CI = 1.15-1.40), liver disease (HR = 66.24; 95%CI = 48.19-91.03) and extrahepatic malignancy (HR = 1.69; 95%CI = 1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death. CONCLUSION: AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.

In vitro analysis of gallstone formation in the presence of bacteria.

AIM: In our previous study, we have isolated different genera of bacteria from gallstones and this intrigued us to study their role in gallstone formation. The isolates exhibited certain biliary activities like urease activity, slime production, and ß-glucuronidase production. We aimed to investigate the role of these factors in the formation of gallstone in in vitro conditions at a supersaturated concentration of cholesterol. METHODOLOGY: To mimic bile in in vitro state, Brilliant Green Bile Broth (BGBB) media having a composition similar to human bile was used. Four different experimental sets were prepared, each having nine flasks with varying concentrations of cholesterol and CaCO3 (calcium carbonate). Test sets I, II, III, and IV were inoculated with Salmonella, Enterococcus, Helicobacter, and Neisseria respectively, which were isolated from gallstone itself. Out of these four bacteria, only Helicobacter did not possess slime activity. A control set was also established which was devoid of bacteria. The control also had nine flasks with different concentrations of cholesterol and CaCO3. All the sets were incubated in the incubator shaker at 37 °C and 80 revolution per minutes (RPM) for 20 days. RESULT: It was observed that the sets having bacteria had a less nucleation time as compared to the control (F = 5.274; p < 0.001). Solidification of gallstone was observed only in the set with bacteria having slime activity (sets I, II, and IV). CONCLUSION: The slime activity of bacteria leads to solidification of gallstones, whereas the other activities accelerate the nucleation of gallstone formation enhancing the severity of the disease.

2019-nCoV: a worldwide concern and facts.

A recent outbreak of endemic disease speeded by a virus whose genome is similar to that of SARS and MERS which outbreak in 2002 and 2012 respectively. All these are zoonotic infection which means these has transmitted from animal to human. Another similarity amongst these infections is that bat is supposed to be primary reservoir for these viruses. 2019-nCoV was reported by WHO on 31 December 2020 which is spreading with alarming rate. WHO has considered this infection as pandemic which means that if the infection is misled then it will spread fear and will cause unnecessary suffering and death. The onset of infection shows general symptoms of flu which later on develops to pneumonia. The main challenge of the infection is that a defined vaccine or medicine is still under trial. Treatment is done on the basis of symptoms and recovery is dependent on the immune response of the patients. This review article is based on meta-analysis of the data where the relation between reproduction number (R0) and infection rate is well depicted. Most of the countries has R0 > 1 which says the infection is epidemic. Symptoms and possible treatment till date is well defined in this paper. Though the COVID-19 virus has changed its strain and came up with asymptomatic infection which is more challenging. Here we present all the relevant information and facts about novel corona virus.

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients.

Precipitants of Acute-on-Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes.

Acute-on-chronic liver failure (ACLF) is a feared complication that can develop at any stage of chronic liver disease. The incidence of ACLF is increasing, leading to a significant burden to both the affected individual and health care systems. To date, our understanding of ACLF suggests that it may be initiated by precipitants such as systemic infection, alcohol use, or viral hepatitis. The prevalence of these vary significantly by geography and underlying liver disease, and these precipitants have a varying impact on patient prognosis. Herein, we present a review of our current understanding of the precipitants of ACLF, including gaps in current data and opportunities for meaningful intervention and areas of future research.