Manifestations Of Chronic Liver Disease Research Articles

Advances in the understanding of the role and mechanism of action of PFKFB3‑mediated glycolysis in liver fibrosis (Review).

Liver fibrosis is a pathophysiologic manifestation of chronic liver disease and a precursor to cirrhosis and hepatocellular carcinoma. Glycolysis provides intermediate metabolites as well as energy support for cell proliferation and phenotypic transformation in liver fibers. 6‑Phosphofructo‑2‑kinase/fructose‑2,6‑bisphosphatase 3 (PFKFB3) is a key activator of glycolysis and plays an important role in the process of glycolysis. The role of PFKFB3‑mediated glycolysis in myocardial fibrosis, renal fibrosis and pulmonary fibrosis has been demonstrated, and the role of PFKFB3 in the activation of hepatic stellate cells by aerobic glycolysis has been proven by relevant experiments. The present study reviews the research progress on the role and mechanism of action of PFKFB3‑mediated glycolysis in the progression of hepatic fibrosis to discuss the role of PFKFB3‑mediated glycolysis in hepatic fibrosis and to provide new ideas for research on PFKFB3 as a target for the treatment of hepatic fibrosis.

Respiratory problems associated with liver disease in children.

Respiratory manifestations of chronic liver disease have a profound impact on patient clinical outcomes. Certain conditions within paediatric liver disease have an associated respiratory pathology. This overlap between liver and respiratory manifestations can result in complex challenges when managing patients and requires clinicians to be able to recognise when referral to specialists is required. While liver transplantation is at the centre of treatment, it opens up further potential for respiratory complications. It is established that these complications place patients at risk of longer stays in hospital and reduced survival. Additionally, late post-transplant complications can occur, including post-transplant lymphoproliferative disease and immunosuppression-induced interstitial lung disease. Although rare, it is important for clinicians to recognise these conditions to allow for prompt management. Finally, as liver disease progresses in children, respiratory complications can occur. Hepatopulmonary syndrome can occur in the context of portal hypertension, resulting in increased mortality and poorer quality of life for patients. Another consequence is portopulmonary hypertension, which can be associated with poor survival. Failure to recognise these complications in children may result in poorer outcomes and therefore it is vital that clinicians can establish when referral to a paediatric respiratory medicine specialist is required.

Serum biomarkers of liver fibrosis identify globus pallidus vulnerability

The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance.

Hepatomusculoskeletal disorders: Coining a new term might improve the management of the musculoskeletal manifestations of chronic liver disease.

Chronic liver disease can affect many body systems including the musculoskeletal system. The pathogenetic crosstalk between the liver and organs such as the brain and the kidneys has already been described with compound terms merging the organs affected by the pathology, such as the hepatorenal syndrome. Nevertheless, the musculoskeletal manifestations of chronic liver disease have not been coined with such a term to date. Because of this shortage, documenting the musculoskeletal implications of chronic liver disease in both research and clinical practice is challenging. To fill this gap, the authors propose the term hepatomusculoskeletal disorders, a compound term of Greek origin that encompasses all the body structures involved in the aforementioned pathologic crosstalk.

Mistakes in assessing the nutrition of patients with chronic liver disease and practical recommendations on how to avoid them: essentials of the United European Gastroenterological Week (2021)

Malnutrition is common for patients with chronic liver disease (CLD), it significantly aggravates prognosis for their quality of life and overall survival. Liver cirrhosis (LC) is one of the most severe CLD manifestations. The main causes of malnutrition at CL include insufficient food intake (deficiency of nutrients, especially proteins), malabsorption, metabolic disorders (predominance of gluconeogenesis rather than glycogenolysis) and changes in substrate metabolism (hypermetabolism). Sarcopenia, which is defined by loss of muscle mass and function, is a major component of malnutrition in patients with cirrhosis. It is important to note that sarcopenia adversely affects the number and severity of complications, quality of life, the outcome of liver transplantation and the overall survival rate of patients with advanced liver disease.Physicians of different specialties should be aware of the clinical and prognostic relevance of nutritional status, how to promptly recognize malnutrition and sarcopenia in patients with liver cirrhosis and how to appropriately manage these conditions.This paper elucidates methods of assessment of the nutritional status of patients and screening for sarcopenia, the main pathogenetic links in sarcopenia development, dietary recommendations (including diet in case of hepatic encephalopathy development), tactics of curation of patients with eating disorders. Particular attention is paid to assessing the presence of eating disorders in the process of selection of patients for transplantation and for TIPS. Recommendations are given for educating the caregivers for patients with chronic liver disease and informing patients about the risks of developing sarcopenia/sarcopenic obesity.This article discusses some of the most common errors in assessing the diet of patients with chronic liver disease, as well as current practical recommendations based on evidence that will allow physicians to avoid possible future errors in the care of such patients.

Association between liver fibrosis and cognition in a nationally representative sample of older adults.

Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults. We examined the association between liver fibrosis and cognitive performance among participants aged 60years and older in the US National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease. Among 3217 adult participants, the mean age was 69years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% [95% confidence interval (CI) 4.0-6.0] had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (β -0.39; 95% CI -0.58, -0.21), language fluency (β -0.46; 95% CI -0.72, -0.21), and attention/concentration (β -1.34; 95% CI -2.25, -0.43), but not delayed recall (β -0.10; 95% CI -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease. Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.

Treatment Options for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing a Scheduled Procedure.

Thrombocytopenia is a consequence of portal hypertension and is the most common hematological manifestation of chronic liver disease (CLD) (ie, cirrhosis). Data indicates the rates of CLD are increasing and, as a result, so will the incidence of this complication. Although bleeding risks are only relevant when elective procedures are performed, this is a frequent concern as these procedures are commonly part of the spectrum of care for patients with cirrhosis. As such, thrombocytopenia remains a pertinent issue. Fortunately, we now have effective and accurate treatment modalities to raise platelet counts before scheduled procedures, known as thrombopoietin receptor agonists. Two drugs in this therapeutic class (avatrombopag and lusutrombopag) are now approved for the treatment of thrombocytopenia in adults with CLD undergoing a procedure and have revolutionized how this is managed. Although there is progress in the field, peer-reviewed literature and expert guidance are lacking. Recognizing these unmet needs, a group of expert hepatologists comprised this review, which summarizes the most current and relevant peer-reviewed literature on thrombocytopenia in CLD and provides clinical expertise on this timely topic.

Pulmonary manifestations of chronic liver disease: a comprehensive review.

Hepatopulmonary syndrome (HPS) and porto-pulmonary hypertension (PoPH) represent relatively common pulmonary vascular complications of advanced liver disease. Despite distinct differences in their pathogenetic background, both clinical states are characterized by impaired arterial oxygenation and limited functional status, and are associated with increased pre-transplantation mortality. Accumulation of ascitic fluid in the pleural cavity, known as hepatic hydrothorax (HH), is another frequent manifestation of decompensated cirrhosis, which may cause severe respiratory dysfunction, depending on the volume of the effusion, the rapidity of its development and its resistance to therapeutic measures. Orthotopic liver transplantation constitutes the only effective treatment able to resolve the pulmonary complications of liver disease. A prioritization policy for liver transplantation has evolved over the past years regarding advanced stages of HPS, yielding favorable outcomes regarding post-transplantation survival and HPS resolution. In contrast, severe PoPH is associated with poor post-transplantation survival. Hence, liver transplantation is recommended only for patients with PoPH and an acceptable reduction in pulmonary pressure values, after receiving PoPH-targeted vasodilating therapy. This review focuses on basic pathogenetic and diagnostic principles and discusses the current therapeutic approaches regarding HPS, PoPH, and HH.

Implications of Manganese in Chronic acquired hepatocerebral degeneration

Neurological symptoms can be one of the over-riding symptoms in patients with liver cirrhosis. Patients can present with subtle changes in mood or neurological function due to hepatic encephalopathy (HE), to more severe presentations including stupor and coma. While HE, in its severe form, can be clinically easy to diagnose, more subtle forms may be more difficult to recognize. Other neurological diseases may indeed be overlooked in the context of cirrhosis or confuse the physician regarding the diagnosis. Chronic acquired hepatocerebral degeneration (CAHD) is an uncommon problem occurring in patients with cirrhosis characterised by a Parkinsonian-like neurological presentation with damage to the brain secondary to manganese (Mn) deposition. Here we describe a case of a patient with a neurological presentation of liver disease with a review of the current CAHD literature. In conclusion, CAHD is a rare condition occurring in liver cirrhosis that should always be considered in patients with neurological manifestations of chronic liver disease.

Coinfection of hepatitis B and hepatitis C virus among chronic liver disease patients in a tertiary care centre

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common cause of chronic liver disease (CLD) worldwide. Coinfection with both HBV and HCV can occur because of shared routes of infection. Therefore, this study was performed to investigate the seroprevalence of HBV and HCV dual infection among patients attending K R hospital, Mysore with underlying CLD manifestations. Materials & Methods: Serum samples from 80 clinically diagnosed chronic liver disease patients attending K R hospital, Mysore was screened for the presence of hepatitis B surface antigen, Anti-HBc IgM, Anti-HBc Ig Gand anti-hepatitis C virus antibodies by ELISA. Serum samples from 15 healthy individuals were also screened. Results: Among 80 chronic liver disease patients, 67 (83.75%) were males and 13 (16.25%) were females. The maximum number of CLD patients was in the age group of 41 – 50 years (41.30%). Alcoholism (72.5%) was the most common risk factor & cirrhosis of liver was the most common clinical presentation (81.25%). 38 (47.5%) cases were HBV positive (positive for any one marker for HBV). HBs Ag was positive in 22 cases, anti-HBc Ig Min 7 cases, anti-HBc Ig Gin 29 cases. 4 (5%) cases were positive for anti HCV. Three (3.75%) cases showed coinfection of HBV & HCV. Conclusion: To prevent the spread of HBV and HCV, people must be educated about these infections and their mode of transmission. All CLD patients should be tested for HBV and HCV to prevent the mortality and morbidity. HBV & HCV coinfection should not be excluded by negative HBsAg status alone.

The Natural History Of Chronic Liver Disease

The natural history of chronic liver disease is that of a slowly progressive course, in most cases evolving over the course of years to decades. The rate of progression varies by disease state and comorbid conditions, but fibrosis advances on average by one stage every 7 to 10 years. While the development of fibrosis is reversible when the underlying etiology is successfully treated, a large number of patients present to medical attention once advanced fibrosis has already developed. The ultimate clinical and pathological manifestation of chronic liver disease is cirrhosis. Cirrhosis has long been clinically divided into “compensated” and “decompensated” disease, with an estimated 12-year survival in compensated disease and 2-year survival in decompensated disease. Additional clinical stratifications have been proposed, including a five-stage model progressing from cirrhosis without portal hypertension (hepatic venous pressure gradient below 10 mm Hg) to cirrhosis with portal hypertension, and then cirrhosis complicated by bleeding or other decompensating events. These clinical stages correspond to a step-wise increase in mortality and, with the presence of more than one decompensating event, the five-year mortality approaches 90%. The major complications of cirrhosis include varices with or without hemorrhage, ascites, hepatic encephalopathy, immune dysfunction, renal impairment, and hepatocellular carcinoma. Liver transplantation has provided an avenue to alter the course and outcomes in chronic liver disease, with graft survival rates that reach 80% at 5 years. This review contains 4 figures, 6 tables and 51 references Key Words: natural history, cirrhosis, mortality, hepatocellular carcinoma, acute-on-chronic liver failure

Dermatological manifestations of chronic liver disease

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The present study was conducted to assess the spectrum of cutaneous changes in chronic liver disease and to assess any correlation between the skin findings and the type of the liver disease.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A total of 100 patients above 18 years of age suffering from chronic liver disease with cutaneous manifestations and attending the Gastroenterology and Dermatology and Venereology department of Gauhati Medical College and Hospital, Guwahati, India during the period from June 2016 to May 2017 were included in the study.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Out of 100 cases, there were 84 males (84%) and 16 females (16%) with the male to female ratio of 5.25:1. Alcoholic liver disease comprised 62% of the patients in the study, other causes being cryptogenic liver disease (14%), chronic hepatitis infection (12%), Wilson’s disease (2%), autoimmune hepatitis (2%), hepatocellular carcinoma (2%), methotrexate induced liver disease (1%) and non-alcoholic steatohepatitis (1%). Most common skin finding was xerosis (62%). Other key findings included nail changes (60%), pigmentary changes (55%), hair changes (50%), jaundice (40%), cutaneous infections (31%), pruritus (27%).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Patients with chronic liver disease can have a wide spectrum of cutaneous manifestations the most important being xerosis, nail changes, pigmentary changes, hair changes, jaundice, infections, pruritus and spider angioma. These changes can give a clue to the presence of the underlying liver disease and its severity. Hence, identifying these signs earlier can lead to prompt diagnosis and effective management of the underlying condition, thereby preventing its complications.&lt;/p&gt;

Reversible cortical blindness in a case of hepatic encephalopathy

Hepatic encephalopathy is a frequent and often fatal manifestation of chronic liver disease. The pathogenesis of hepatic encephalopathy is believed to be multifactorial including impaired blood-brain barrier function, imbalance between the excitatory and inhibitory neurotransmitters in cortex, accumulation of various toxic and false neurotransmitters, and lack of nutrients like oxygen and glucose. Signs and symptoms of hepatic encephalopathy varies and commonly ranges from personality changes, disturbed consciousness, sleep pattern alternation, intellectual deterioration, speech disturbances, asterixis to frank coma and even death. Reversible or transient cortical blindness is rare manifestation of hepatic encephalopathy. It may even precede the phase of altered consciousness in such patients. Very few similar cases have been reported worldwide. Hence, we would like to report a case of transient cortical blindness in a patient of hepatic encephalopathy.

The senescent hepatocyte gene signature in chronic liver disease

Hepatocyte senescence is associated closely with fibrosis stage and an adverse outcome in chronic liver disease, but it is uncertain whether there is a causal relation with clinical manifestations of chronic liver disease, which was the subject of this study of the senescent hepatocyte gene signature. Senescence was induced in HepG2 cells using sub-lethal concentrations of H2O2. Gene expression of control and senescent HepG2 cells were studied. Comparison was made with patients with cirrhosis and three public microarray datasets. H2O2-treated HepG2 cells demonstrated characteristic cellular senescence. There was differential expression of 354 genes in senescence. Up-regulated genes in HepG2 senescence were also up regulated in patients with cirrhosis. The senescent hepatocyte gene signature distinguished liver disease from normal by unsupervised clustering in the public chronic liver disease microarray datasets, with enrichment of the senescence gene signature in all three datasets. The senescent hepatocyte gene signature included changes in cell cycle regulation, morphology, inflammation, signal transduction, metabolism and stellate cell activation, which alongside impaired synthetic function in senescence in vitro were consistent with manifestations of clinical liver disease, suggesting a close relation between hepatocyte senescence and manifestations of chronic liver disease including fibrosis and impaired synthetic function.

Regulation of gene expression by microRNA in HCV infection and HCV–mediated hepatocellular carcinoma

MicroRNA (miRNA) exert a profound effect on Hepatitis C virus (HCV) replication and on the manifestation of HCV-associated hepatocellular carcinoma (HCC). miR-122 in particular, is highly enriched in liver and has been shown to interact with HCV, suggesting this virus has evolved to subvert and manipulate the host gene silencing machinery in order to support its life cycle. It is therefore likely that miR-122 and other miRNAs play an important role in the pathophysiology of HCV infection. The changes in post-transcriptional gene regulation by the miRNAs may play a key role in the manifestation of chronic liver disease and hepatocellular carcinoma. Understanding of HCV-host miRNA interactions will ultimately lead to the design of therapeutic modalities against HCV infection and HCV-mediated HCC and may also provide important biomarkers that direct treatment options. Here, we review the current knowledge on the role of miRNA and gene expression on HCV infection and hepatocellular carcinoma, in addition to the possible role of miRNA as future therapeutic targets.

Fatal Hyperammonemic Encephalopathy after Gastric Bypass

Purpose: A 43-year-old female with a history of Roux-en-Y Gastric Bypass performed 10 years ago presented with abdominal pain and lower extremity edema. A CT scan showed a distended remnant gastric pouch. Upper endoscopy was performed showing a normal esophagus without esophageal varices and ulceration at the gastro-jejunal anastomosis. The remnant stomach and a small portion of the duodenum were excised for a suspected gastro-gastric fistula. Pathology showed chronic gastritis, chronic duodenitis and gastric mucosal ulceration with reparative changes and no Helicobacter pylori infection. The patient was discharged and was subsequently admitted for purulent drainage from her surgical wound. Cultures grew enterobacter and she was started on the appropriate antibiotics with confirmed laboratory sensitivity. Her mental status suddenly became increasingly altered and she became combative. On physical exam, she had icteric sclera and jaundice with no manifestations of chronic liver disease. She had a direct hyperbilirubinemia with an ammonia level of 191 UMOL/L. Laboratory evaluation did not reveal any deficiencies in thiamine, vitamin B12, folate, copper, or zinc. Vitamin D was low with a value of 17.8 NG/mL. Imaging studies revealed hepatic steatosis with no evidence of biliary obstruction. She was started on lactulose and rifaximin through a naso-gastric tube and also given lactulose enemas. She was also started on daily intravenous thiamine. Imaging of the head and lumbar puncture were normal. She had a rapid deterioration and required intubation shortly thereafter. Despite treatment with lactulose and rifaximin, her ammonia continued to remain extremely high. She required high doses of vasopressors and developed global anoxic brain injury. The family decided to take comfort care measures at that time. The differential diagnosis for non-hepatic hyperammonemia includes medications, hyperalimentation, infections with urease producing bacteria (ex. Helicobacter pylori), surgery induced nutritional deficiencies and errors of metabolism. All potentials in the differential had been excluded for this patient except errors of metabolism. An exceedingly rare phenomenon with a nearly identical presentation has been previously described involving female patients developing fatal hyperammonemic encephalopathy after gastric bypass surgery, some as much as 28 years after their surgery. The mechanism remains unknown, but is thought to involve the unmasking of inborn errors of urea metabolism, the most common of which is ornithine transcarbamylase deficiency. Clinicians and bariatric centers must become more aware of this new phenomenon as more studies are needed to reveal its natural history and underlying cause.

Pulmonary Manifestations of Chronic Liver Disease

Pulmonary Manifestations of Chronic Liver Disease

Pulmonary manifestations of chronic liver disease.

Several lung disorders can occur as a consequence of chronic liver disease. In addition to the common findings of splanchnic and systemic vasodilatation in patients with chronic liver disease, pulmonary vasodilatation may also occur. This "hepatopulmonary syndrome' results in hypoxemia through pulmonary vasodilation and VA/Q mismatch, and in its advanced form leads to significant intrapulmonary arteriovenous shunting. Portal hypertension commonly results in the development of ascites, which may cause a restrictive lung pattern or pleural effusions. Rarely, thrombi formed in congested portal vein branches pass through portosystemic shunts and cause pulmonary hypertension, and plexogenic pulmonary hypertension may also occur in patients with portal hypertension. The autoimmune liver diseases, primary biliary cirrhosis and autoimmune hepatitis, may be accompanied by immune-mediated lung disease. These pulmonary abnormalities represent important extrahepatic manifestations of chronic liver disease.

5 Autoantibodies

The number of autoantibodies associated with chronic liver disease continues to burgeon and characterization of these immunoreactivities will undoubtedly enhance understanding of the autoantigens that are targeted by cytodestructive immunocytes. Assays for the majority of these immunoserological species are not generally available and in most instances, assessments are restricted to individual laboratories with vested interests in characterizing a particular species. For clinical diagnosis and management of autoimmune liver disease, assays for ANA, SMA, anti-LKM1 and AMA are essential. This conventional armamentarium, however, must be upgraded on a regular basis to ensure availability and application of the most useful assays. Unfortunately, there are no formal mechanisms for improving the diagnostic resources and standardizing testing strategies. An important first step must be taken by the basic laboratories that advocate individual assay systems. These facilities must share methodologies and exchange serum samples so that the most clinically pertinent and cost-effective immunoserological batteries can be defined and promulgated. Industry can then respond to need and facilitate the commercialization of assays for general use. Currently, the assays that warrant dissemination are those that detect antibodies to the E2 subunits of the pyruvate dehydrogenase complex and antibodies to asialoglycoprotein receptor. Both assays have high diagnostic specificity and each reflects reactivity to an important target autoantigen of probable pathogenic importance. Each autoantibody species can supplant conventional assays such as those for AMA and ANA and they each may impart useful clinical information. In the case of antibodies to the E2 subunits, titres may reflect histological progression of PBC. In the case of antiASGPR, disappearance of the autoantibodies in patients with autoimmune hepatitis may secure a confident treatment end-point. Great progress has been made in defining the immunoserological manifestations of chronic liver disease but little has been done to distribute the resources.

Clinical Manifestations of Chronic Liver Disease, Clinical Teaching Project. American Gastroenterological Association. Mini–Unit A. by C.A. Riely and R.S. Koff. Timonium, Md: Milner–Fenwick, Inc., 1993. $25

Clinical Manifestations of Chronic Liver Disease, Clinical Teaching Project. American Gastroenterological Association. Mini–Unit A. by C.A. Riely and R.S. Koff. Timonium, Md: Milner–Fenwick, Inc., 1993. $25