Biomarkers of Liver Cirrhosis

This report describes extrahepatic bile duct obstruction in two ferrets, which were presented
with anorexia, chronic weight loss and general weakness. Physical examination revealed lethargy,
cachexia, dehydration, abdominal pain and icterus. Marked haematological, serum chemistry and
urinalysis abnormalities included hyperbilirubinaemia (65·5 and 114·2 μmol/L), high concentrations
of alanine transaminase (1327·53 and 2578·88 IU/L) and biluribinuria. Abdominal ultrasonography
revealed thickening of the bile duct together with the gall bladder wall. The common bile duct was
obviously distended. Choledochotomy revealed inspissated bile with fragile green gelatinous plugs
that was removed to allow the bile to flow into the duodenum. Cytology and culture of the biliary tract
contents were negative for bacteria. Laboratory analyses of biliary plugs showed presence of only protein
substances, without detectable mineral composition. Histopathological examination of the liver
showed diffuse steatosis and non-specific cholangiohepatitis in both cases.

Hepatocellular carcinoma (HCC) is increasing in prevalence and has the potential to be a highly lethal malignancy. Patients with early-stage HCC have potentially curative therapeutic options, but treatments for more advanced HCC were limited until recently. Historically, tyrosine kinase inhibitors have been used in both the first-and second-line treatment of patients with advanced HCC; however, given HCC's highly immune-responsive origins, immunotherapy is proving to be a promising systemic therapy in the frontline as well as later lines of treatment. Notably, recent studies of the novel antibody therapy combination atezolizumab (anti-PD-L1) and bevacizumab demonstrated unprecedented, practice-changing efficacy in the advanced HCC setting and led to its Food and Drug Administration approval. Although such landmark studies offer new treatment options for patients with HCC, the role of potential biomarkers to monitor immunotherapy response is largely unknown and undergoing exploration.

Background: Detecting early signs of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) during the pre-symptomatic phase is becoming increasingly important for costeffective clinical trials and also for deriving maximum benefit from currently available treatment strategies. However, distinguishing early signs of MCI from normal cognitive aging is difficult. Biomarkers have been extensively examined as early indicators of the pathological process for AD, but assessing these biomarkers is expensive and challenging to apply widely among pre-symptomatic community dwelling older adults. Here we propose assessment of social markers, which could provide an alternative or complementary and ecologically valid strategy for identifying the pre-symptomatic phase leading to MCI and AD. Methods: The data came from a larger randomized controlled clinical trial (RCT), where we examined whether daily conversational interactions using remote video telecommunications software could improve cognitive functions of older adult participants. We assessed the proportion of words generated by participants out of total words produced by both participants and staff interviewers using transcribed conversations during the intervention trial as an indicator of how two people (participants and interviewers) interact with each other in one-on-one conversations. We examined whether the proportion differed between those with intact cognition and MCI, using first, generalized estimating equations with the proportion as outcome, and second, logistic regression models with cognitive status as outcome in order to estimate the area under ROC curve (ROC AUC). Results: Compared to those with normal cognitive function, MCI participants generated a greater proportion of words out of the total number of words during the timed conversation sessions (p=0.01). This difference remained after controlling for participant age, gender, interviewer and time of assessment (p=0.03). The logistic regression models showed the ROC AUC of identifying MCI (vs. normals) was 0.71 (95% Confidence Interval: 0.54 – 0.89) when average proportion of word counts spoken by subjects was included univariately into the model. Conclusion: An ecologically valid social marker such as the proportion of spoken words produced during spontaneous conversations may be sensitive to transitions from normal cognition to MCI.

Despite the development of surrogate non-invasive methods, histological evaluation remains an important tool for reliable classification, grading and staging, as well as prognosis in non-alcoholic fatty liver disease (NAFLD). However, histological evaluation has been criticised because it requires a liver biopsy, its propensity for sampling, and inter-observer variation. This article highlights the future developments in the morphological interpretation of liver biopsy in NAFLD, so as to aid in improving its diagnostic and prognostic utility.

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis and staging.

Methods: A systematic literature search was conducted on any relevant database or institutional website to find guidelines on NAFLD assessment intended for clinical use on humans, in English, published from January 2010 to August 2020. Included guidelines were appraised using the AGREE II Instrument; those with higher scores and intended for use in adult patients were included in a comparative analysis.

Results: Fourteen guidelines were included in the systematic review, eight of which reached an AGREE II score sufficiently high to be recommended for clinical use, of which one developed for pediatric patients only. British and North American guidelines received the highest scores. Most guidelines recommend a screening or case-finding approach in patients with metabolic risk factors who are at increased risk of steatohepatitis or fibrosis. Ultrasound  is mostly recommended to confirm steatosis, while the presence of metabolic syndrome, liver function tests, fibrosis scores, and elastographic techniques may help in selecting high-risk patients to be referred to the hepatologist, who may consider liver biopsy, although referral criteria for liver biopsy are not clearly defined. Most guidelines identify the development of noninvasive tests to replace liver biopsy as a research priority.

Conclusion: Several high-quality guidelines exist for NAFLD assessment, with no complete agreement on whether to screen high-risk patients and on the tests and biomarkers suggested to stratify patients and select those to be referred to liver biopsy.

Autoimmune hepatitis is characterized by a continuing hepatocyte necrosis that usually progresses to liver cirrhosis. Autoimmunity is also a feature of chronic infection by Helico-bacter pylori, a gram-negative bacterium involved in the pathogenesis of peptic ulcer and upper gastrointestinal bleeding, with both events frequently occurring in patients with chronic liver disease. A newly described pathogenetic mechanism for chronic hepatitis and hepato-cellular carcinoma in the mouse is linked to Helicobacter spp. infection. A high prevalence of H. pylori infection was demonstrated in patients with viral-related cirrhosis but never studied in cases of autoimmune hepatitis. In a case-control study, we examined 31 consecutive patients (25 women and 6 men, age range 20 – 66, mean age 46 4.3 years) suffering from autoimmune hepatitis and 62 sex-and age-matched blood donors (50 women, 12 men, age range 20 – 65, mean age 46 5.4 years) resident in the same area. Antibodies to H. pylori were present in 20 of 31 (64.5%) autoimmune patients compared to 33 of 62 (53.2%) controls (P 0.3, odds ratio 1.60, 95% CI 0.60 – 4.28). The difference was not statistically significant either in female or male patients. In conclusion, the prevalence of H. pylori infection in patients and controls was similar in our study of patients with chronic autoimmune hepatitis.

Globally, hepatocellular carcinoma (HCC) is associated with a poor prognosis due to frequent diagnosis in late stages. As a result, mortality is roughly equivalent to the annual incidence. Regardless of etiology, the development of liver cirrhosis is the most relevant cause of hepatocarcinogenesis. Chronic hepatitis B virus (HBV) infection and nonalcoholic steatohepatitis (NASH) are associated with a significantly increased risk of developing HCC even in the absence of cirrhosis. Recent data demonstrate that NASH has to be considered as the main cause of the increasing incidence of HCC predicted for the next decades. Thus, against the background of high mortality, the need for optimized HCC screening strategies arises on the one hand, while, on the other hand, previous treatment concepts have to be adapted to the sometimes therapy-limiting comorbidities of these patients.

** Faculty of Pharmacy, Cairo University.
[email protected]
Abstract
Seventy five samples of frozen meat, raw milk and poultry feed (25 samples each), were examined mycologically and for detection of aflatoxin B1 (AFB1). The results revealed that the isolated fungi represented 6 genera of moulds. The most prevalent fungi in these samples was the genus aspergillus (60%, 60% and 76%) with mean of count of (1.6 x 102 ± 0.1, 6.0 x 10 ± 0.23 and 3 x 102 ± 1.0), respectively, which was at the top of all isolated fungi . However, A. flavus was isolated form all kind of samples and that which isolated from feed produced aflatoxin B1 with mean level of (60 ± 0.1 ppb) followed by that isolated from frozen meat (9.5 ± 0.71 ppb), but those isolated from milk had the lowest AFB1 level (1.0 ± 0.1 ppb). The effect of dimethyl 4, 4- dimethoxy 5, 6, 5, 6- dimethylene dioxybiphenyl 2, 2- dicarboxylate (D.D.B.) in degradation of AF was evaluated by intraperitoneal injection of 30 rats with 1.5 ppm of AFB1 to evaluate their effect on haematological, biochemical and protein electrophoretic patterns of aflatocicated rats. The obtained results indicates an improvement in the haematological picture (Hb, RBCs and PCV) together with WBCs and differential leucocytic count of the treated rats compared with non treated ones. Also, biochemical analysis revealed significant changes in urea and creatinine levels; AST and ALT activities; total protein and protein electrophoretic patterns of treated rats. The administrated of DDB effectively improved haematological alterations and prevent serum biochemical changes, ameliorated, the toxic effect of aflatoxin B1 and had hepatoprotective effect on AFB1 induced liver toxicity. [Life Science Journal 2010;7(3):148-153]. (ISSN: 1097-8135).
Keywords: frozen meat; raw milk; poultry feed; aflatoxin B1 (AFB1); genus aspergillus; toxicity