Complication Of Chronic Liver Disease Research Articles

Management strategies for chronic liver disease-related thrombocytopenia

Chronic liver disease causes bleeding and coagulation system abnormalities through a variety of mechanisms. Thrombocytopenia is a common complication of chronic liver disease. Patients with chronic liver disease, especially liver cirrhosis, often face more invasive examinations or surgeries, which brings great challenges to clinical diagnosis and treatment. Traditional platelet transfusion is the main clinical intervention. With the approval of thrombopoietin receptor agonists, the current management standards for chronic liver disease-related thrombocytopenia may face changes. This article reviews the current main non-pharmacological and pharmacological interventions for chronic liver disease-related thrombocytopenia, and put forwards the corresponding clinical management improvement strategies based on the efficacy and limitations of these interventions.

Chronic Liver Diseases- Experience at Tertiary Care Centre of Northern India

Introduction: It is important to determine the epidemiological factors like etiology, age, sex, mode of clinical presentation and pattern of development of complications of chronic liver disease, so as to design optimal and cost effective preventive and treatment strategies for the same. Aim: To determine etiology of Chronic liver disease in Northern India. Material and Methods: This was a prospective study done at Medical Gastroenterology Department, PGIMS,Rohtak conducted over a period of ten years i.e. 01.01.2011 to 31.12.2020, on 1000 confirmed patients of chronic liver disease (CLD). Results: The most common etiology seen was Alcoholic liver disease (48.9%), followed by Nonalcoholic liver disease (26.4%), Chronic Hepatitis B (12.3%), Chronic Hepatitis C (9%), Cryptogenic (2.7%) and Autoimmune liver disease related (0.7%). Conclusion: The present study reveals that alcohol is most common cause of chronic liver disease in Northern India. The males of middle age group with rural background are at significant risk of developing CLD, thus requiring immediate social and medical intervention.

P-15 WAITING LIST FOR LIVER TRANSPLANTATIOS: CLINICAL AND ECONOMIC BURDEN, RETROSPECTIVE STUDY

Burden of disease is an indicator that relates to health status. United States (US) and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37 ± 3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3565), followed by spontaneous bacterial peritonitis ($2576) and variceal hemorrhage ($1530). The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

Role of Flash Glucose Monitoring System in Diabetic Patients with Chronic Liver Disease

Background: Diabetic patients show serious complications of chronic liver disease. The monitoring of glucose in diabetic patients with chronic liver disease is very challenging. Generally, the glycaemic control monitoring in chronic liver disease patients is the same as in a person who does not have any liver disease. Flash glucose monitoring system is a way to measure glucose levels of body without pricking the body. It is an innovative method of measuring glucose levels. A flash glucose monitor is a small sensor. This sensor is a small sticky chip and is attached on the skin of the arm. One side of the chip has a small needle that goes inside the skin. It records glucose levels throughout day and night continuously. Levels of glucose can be assessed whenever wanted. Materials and Methods: The study was conducted in the Medical Ward 1, Bahawal Victoria Hospital, Bahawalpur and the Department of Pathology, Quaid-e-Azam Medical College, Bahawalpur from 1st January 2018 to June 2020. Freestyle Libre Sensor flash glucose monitoring system (by CoolPlus Medical) was used to measure glucose of subcutaneous interstitial fluid. The disposable sensor was applied to the back of the arm for up to 14 days. Sensor is calibrated by the factory with no automatic alarms. Results: We noticed that the results of the patients who had co-existing disease of chronic hepatitis and diabetes mellitus had same results of glucose readings when measured by flash glucose monitoring system and by finger prick for glucose measurement by glucometer. Conclusion: Flash glucose monitoring system is way better than self monitoring blood glucose method by glucometer in diabetic patients with chronic liver disease. Keywords: Diabetes, glucose, monitoring, chronic liver disease, complications

Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology.

Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400ng/mL (N=542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazard model (stratified by study). Baseline characteristics were generally balanced between arms in each subgroup (HBV: N=225, HCV: N=127, Other: N=190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P-value = .23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55-0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55-1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40-0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver-specific adverse events. Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.

Hepatic Hydrothorax in the Absence of Ascites: A Diagnostic Challenge

Hepatic hydrothorax is a rare complication of chronic liver disease. It usually occurs in patients with advanced liver disease, portal hypertension, and ascites. On a rare instance, it may be the index presentation of chronic liver disease. Hepatic hydrothorax occurs in approximately 5-6% of patients with cirrhosis. The exact mechanism has not been well defined, but it is frequently thought to be due to the direct passage of ascitic fluid from the peritoneal cavity through the diaphragmatic defects. Treatment involves salt and water restriction and diuretics. Therapeutic thoracocentesis is required in case of respiratory distress. In resistant cases, indwelling pleural catheter (IPC) like PleurX catheter system (Franklin Lakes, NJ: BD) is placed and patients manage their symptoms through intermittent drainage of the pleural fluid. Here we describe an unusual case of hepatic hydrothorax in a patient with rheumatoid arthritis and liver cirrhosis without any ascites, a scenario that has rarely been reported in the literature. The patient underwent thoracentesis thrice but in view of re-accumulating pleural effusion, a pig-tail catheter with underwater seal was inserted. She was then referred to a hepatology center for transjugular intrahepatic portosystemic shunt (TIPS) or liver transplant.

Minimal hepatic encephalopathy may be present despite the absence of non-invasive and elastography evidence of cirrhosis in patients with primary biliary cholangitis

PurposeMinimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis. Patients and methodsFifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score. ResultsMHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC ​= ​0.753, CI95% ​= ​0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE. ConclusionsMHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC.

Platelet Response to Lusutrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease and Thrombocytopenia Undergoing Non-Emergency Invasive Procedures: Results from a Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

Thrombocytopenia is a common complication of chronic liver disease (CLD), which may be caused by multiple factors including decreased production of thrombopoietin (TPO). The presence of thrombocytopenia may complicate the conduct of routine invasive procedures that are commonly performed in CLD patients, leading to delayed or cancelled procedures. Lusutrombopag (formerly S-888711) is an orally available, small molecule agonist of human TPO receptor. Here we report the platelet response data from a confirmatory global phase 3, randomized, double-blind, placebo-controlled study (L-PLUS 2 study) evaluating lusutrombopag for the treatment of thrombocytopenia in patients with CLD who were undergoing non-emergency invasive procedures.Key eligibility criteria included 18 years of age or older, platelet count < 50 × 109/L at baseline, Child-Pugh Class A or Class B, and expecting to undergo a non-emergency invasive procedure. Patients with existing or history of portal vein thrombosis (PVT), or with past or present thrombosis or prothrombotic conditions were excluded. Patients were randomized 1:1 to receive oral lusutrombopag 3 mg once daily or placebo for up to 7 days. Stopping criteria based upon platelet count measurement on days 5, 6 and 7 were used to prevent platelet overshoot. Invasive procedures were performed between Day 9 and Day 14. Platelet transfusion was mandated by the study protocol if a patient's platelet count prior to the invasive procedure was < 50×109/L. The primary efficacy endpoint was proportion of patients who require no platelet transfusion prior to the primary invasive procedure and no rescue therapy for bleeding from randomization to 7 days after the primary procedure. Safety assessment included adverse events, physical exams, laboratory tests and imaging for detection of PVT.A total of 215 patients were randomized, constituting the ITT population (lusutrombopag 108, placebo 107). Baseline patient characteristics were similar between the two treatment groups. The most common invasive procedures included endoscopic variceal ligation (28%), endoscopy with or without polypectomy/biopsy (27%), dental extraction (11%), and transarterial chemoembolization (9%). The study met its primary efficacy endpoint: 64.8% of patients in lusutrombopag group required no platelet transfusion prior to their procedures and no rescue therapy for bleeding up to 7 day after the procedure, compared to 29.0% of patients in the placebo group (p<0.0001). The proportion of patients who met the definition of platelet responder (platelet count ≥ 50×109/L and an increase from baseline of ≥ 20×109/L at least once during the study) was 64.8% in lusutrombopag group and 13.1% in placebo group (p<0.0001). Figure 1 shows the median platelet count over the study period for both treatment groups. Among patients in the lusutrombopag group who did not receive platelet transfusion, the mean peak platelet count was 86.9×109/L (mean increase from baseline 47.1×109/L) which occurred on average around Day 12, and the median duration of platelet count maintained at ≥ 50×109/L was 19 days. Treatment-emergent adverse events (TEAEs) were reported for 47.7% of patients in lusutrombopag group and 48.6% in placebo group, with serious TEAEs at 6.5% in each treatment group. Three PVT events were observed, 1 in lusutrombopag group and 2 in placebo group; all were incomplete occlusion considered not clinically significant and all events resolved with therapy. Bleeding-related TEAEs occurred in 3 patients of lusutrombopag group and 6 patients in placebo group.In conclusion, oral lusutrombopag 3 mg once daily demonstrated superiority over placebo as treatment for thrombocytopenia in patients with CLD undergoing invasive procedures in this global phase 3 study, meeting all pre-specified primary and secondary endpoints. Lusutrombopag was well tolerated, with a safety profile similar to that of placebo. [Display omitted] DisclosuresAfdhal:Shionogi: Consultancy; Merck: Consultancy; Ligand: Consultancy; Jansen: Consultancy; Gilead: Consultancy; Echosens: Consultancy; Spring Bank Pharmaceuticals: Employment, Equity Ownership; Allurion: Equity Ownership; TRIO Healthcare: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Duggal:Shionogi: Consultancy. Ochiai:Shionogi: Employment. Motomiya:Shionogi: Employment. Kano:Shionogi: Employment. Nagata:Shionogi: Employment. Peck-Radosavljevic:Shionogi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Jansen: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Takeda: Research Funding.

Novel Agents in the Management of Hepatic Encephalopathy: A Review.

Hepatic encephalopathy is an often devastating complication of chronic liver disease, associated with high mortality and increased burden on patients and healthcare systems. Current agents (such as nonabsorbable disaccharides and oral antibiotics) are often only partially effective and associated with unpleasant side effects. With our improved understanding of the pathophysiology of hepatic encephalopathy, multiple treatment modalities have emerged with promising results when used alone or as an adjunct to standard medications. The mechanisms of these agents vary greatly, and include the manipulation of gut microbial composition, reduction of oxidative stress, inhibition of inflammatory mediators, protection of endothelial integrity, modulation of neurotransmitter release and function, and other novel methods to reduce blood ammonia and neurotoxins. Despite their promising results, the studies assessing these treatment modalities are often limited by study design, sample size, outcome assessment heterogeneity, and paucity of data regarding their safety profiles. In this article, we discuss these novel agents in depth and provide the best evidence supporting their use, along with a critical look at their limitations and future directions.

Neinvazivní metody v posuzování závažnosti portální hypertenze

Portal hypertension represents a wide spectrum of complications of chronic liver diseases and may present by ascites, oesophageal varices, splenomegaly, hypersplenism, hepatorenal and hepatopulmonary syndrome or portopulmonary hypertension. Portal hypertension and its severity predicts the patient‘s prognosis: as an invasive technique, the portosystemic gradient (HPVG – hepatic venous pressure gradient) measurement by hepatic veins catheterisation has remained the gold standard of its assessment. A reliable, non-invasive method to assess the severity of portal hypertension is of paramount importance; the patients with clinically significant portal hypertension have a high risk of variceal bleeding and higher mortality. Recently, non-invasive methods enabling the assessment of liver stiffness have been introduced into clinical practice in hepatology. Not only may these methods substitute for liver biopsy, but they may also be used to assess the degree of liver fibrosis and predict the severity of portal hypertension. Nowadays, we can use the quantitative elastography (transient elastography, point shear-wave elastrography, 2D-shear-wave elastography) or magnetic resonance imaging. We may also assess the severity of portal hypertension based on the non-invasive markers of liver fibrosis (i.e. ELF test) or estimate clinically signifi cant portal hypertension using composite scores (LSPS – liver spleen stiff ness score), based on liver stiffness value, spleen diameter and platelet count. Spleen stiffness measurement is a new method that needs further prospective studies. The review describes current possibilities of the non-invasive assessment of portal hypertension and its severity.

Evaluation of the Difference between Cirrhotic Patients Receiving Propranolol and Those Receiving Propranolol Plus Losartan in terms of Renal Artery Resistive Index

Introduction: Portal hypertension is one of the main clinical complications of chronic liver diseases. In only 30% of cirrhotic patients who take propranolol, the hepatic venous pressure reduces to under 12 mm/Hg. The results of studies on the efficiency of losartan (an angiotensin II receptor antagonist) in reducing portal hypertension have been controversial so far. Hepatic venous pressure gradient (HVPG) is measured using an invasive method of catheterization. Studies have shown that the measurement of the renal resistive index (RI) by Doppler ultrasonography has a direct relationship with HVPG. The study population included cirrhotic patients who referred to Ali-ibn-Abi Talbe Clinic, Zahedan, Iran. This clinical trial was conducted based on a self-controlled method. Materials and Methods: In total, 30 cirrhotic patients who met the inclusion criteria were selected for the study. The patients were treated with propranolol 10 mg twice a day for one month, and losartan was then added to their medication regimen. The renal RI of patients was measured before and after losartan administration. Results: The mean of renal RI of patients treated with both propranolol and losartan (0.659±0.58) was higher than that of the patients treated with only propranolol (0.635±0.597) (P=0.005). Conclusion: Our results showed that cirrhotic patients who received propranolol had high renal RI before and after receiving losartan. Accordingly, it seems that losartan had no effects on reducing HVPG hypertension in patients taking propranolol.

Hepatitis Delta Virus Epidemiology in the Industrialized World.

Within the hepatitis virus landscape, one incomplete virus, the hepatitis delta virus (HDV), appears to differ from hepatitis B and C viruses in the context as it still may not infrequently lead to complications of chronic liver disease and continues to be associated with significant liver-related mortality even when patients have received available treatment for it. Breakthrough therapies are so far lacking for HDV-infected patients and treatment has not changed since the discovery of HDV in 1977 and consists mainly of interferons. While there was little interest on the global epidemiology of HDV until recently, this has changed in the past 2 years and we are currently observing a stream of papers on the global epidemiology of HDV and commentaries about why prevalence estimates appear to differ so dramatically. This may be related to the fact that reliable data are not available for most of the countries. However, in the industrialized world, data on the epidemiology of HDV are expected to be of better overall quality. Hence, this review was undertaken to provide a detailed overview on the epidemiology of HDV infection in industrialized countries using data from representative larger countries. In industrialized countries, with maybe the exception of China, HDV infection is a disease of high-risk groups. Migrant groups and people who inject drugs are the most encountered high-risk groups. This review summarizes the dynamics of their contribution to the HDV epidemiology in industrialized countries of the west and the east.

Is L-ornithine-L-aspartate Effective in Hepatic Encephalopathy? or is it Just a Myth?

Hepatic Encephalopathy (HE), a complication of chronic liver disease, presents with neurological and psychiatric symptoms. It has four grades. Minimal Hepatic Encephalopathy (MHE) is the mildest form of HE. Over the last two decades, many Randomized Controlled Trials (RCTs) have been performed to understand the role of various treatments in HE. L-Ornithine L-aspartate (LOLA) has also been studied. It is a stable salt of two amino acids; L-Ornithine and L-aspartate. It acts in the liver to help utilize extra ammonia by the urea cycle and hence lowers the ammonia levels. This review aims to understand the role of LOLA in HE, MHE, and as a prophylaxis. PubMed was used as a search engine. A total of seven articles were retrieved. Our results demonstrated that LOLA can be very effective in lowering the ammonia levels and hence is not only effective for MHE and prophylaxis, but can play a very significant role in the treatment of HE.

Acute kidney injury in hospitalized cirrhotic patients: Risk factors, type of kidney injury, and survival.

Background and AimAcute kidney injury (AKI) is a common complication of chronic liver disease (CLD). We performed a prospective study to evaluate the risk factors and spectrum of AKI among decompensated cirrhosis (DC) patients and the impact of AKI on survival.MethodsThis study was conducted in consecutive DC patients hospitalized in SCB Medical College between December 2016 and October 2018. AKI was defined as per ICA criteria. Demographic, clinical, and laboratory parameters and outcomes were compared between patients with and without AKI.ResultsA total of 576 DC subjects were enrolled, 315 (54.69%) of whom had AKI; 34% (n = 106) had stage 1A, 28% (n = 90) stage 1B, 21% (n = 65) stage 2, and 17% (n = 54) stage 3 AKI. Alcohol was the predominant cause of CLD (66.7%). In 207 (65.7%) patients, diuretic/lactulose/nonsteroidal anti‐inflammatory drugs use was noted, and infection was present in 190 (60.3%) patients. Compared to those without AKI, patients with AKI had higher leucocyte count, higher serum urea and creatinine, higher Child‐Turcotte‐Pugh, higher Model of End‐Stage Liver Disease (MELD) scores (P < 0.001), longer hospital stay, and lower survival at 28 days and 90 days (P < 0.001). Besides, in patients with stages 1A to 3 AKI, there were differences in overall survival at 28 days (P < 0.001) and 90 days (P < 0.001).ConclusionsOver half of DC patients had AKI, and alcohol was the most common cause of cirrhosis in them. Use of AKI‐precipitating medications was the most common cause of AKI, followed by bacterial infection. AKI patients had increased prevalence of acute‐on‐chronic liver failure and had prolonged hospitalization and lower survival both at 28 days and 90 days.

Hepatocellular carcinoma from the view of gastroenterologist/hepatologist

Hepatocellular carcinoma (HCC) is one of the major complications of chronic liver disease, mostly of liver cirrhosis. Liver diseases from different causes differ in the risks of HCC development. Different mechanisms of carcinogenesis are involved in HCC development in different liver diseases as well. Generally, two main pathways are distinguished: the cause of liver disease itself (e.g. viral infections, accumulation of heavy metals etc.) and chronic liver inflammation and fibrogenesis, including mechanisms of oxidative stress. Rare cases of HCC in liver without underlying cirrhosis are likely the consequences of the mechanisms directly linked with particular etiological factor (e.g. protein X in chronic hepatitis B virus (HBV) infection). The key approach which can lead to significantly better results of any treatment used in HCC cases is HCC screening and surveillance. The appropriate method of HCC surveillance is abdominal ultrasonography in 6-month intervals. There is still one question to be solved: the correct definition of target population which should undergo this method of surveillance. Currently, the target population in the developed world is defined as all patients with liver cirrhosis. Unfortunately, the only method of primary prevention of HCC is available: universal HBV vaccination. Antiviral treatment of hepatitis B or C is considered as a method of secondary prevention. Adjuvant therapy of HCC after its primary therapy (antiviral therapy after HCC resection etc.) and other measures able to reduce HCC recurrence risk are usually mentioned as tertiary prevention approach. The BCLC staging system is the most common system used in Europe for the classification of HCC at the dia-gnosis. This classification combines the stage of HCC itself with other parameters, such as liver disease severity (Child - Pugh classification), portal hypertension etc. BCLC is a system which guides the physicians to optimal treatment options in every HCC stage. The only potentially curable approaches are surgical resection or liver transplantation. These options may be used in 1/3 of all HCC patients. Unfortunately, the vast majority of HCC patients can be treated only by palliative treatment options with transarterial chemoembolisation being the most common one.

Modeling Outcomes in Children With Biliary Atresia With Native Liver After 2 Years of Age.

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%‐30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health‐supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0‐13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%‐32.0%). Twenty‐seven experienced either new‐onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%‐29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C‐index of 0.88 (range, 0.86‐0.89). A cause‐specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C‐index of 0.81 (range, 0.80‐0.84). Internal model validity was assessed using Harrell’s C‐index with cross‐validation. Conclusion: Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials.

Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications.

The liver is a crucial metabolic organ that has a key role in maintaining immune and endocrine homeostasis. Accumulating evidence suggests that chronic liver disease might promote the development of various cardiac disorders (such as arrhythmias and cardiomyopathy) and circulatory complications (including systemic, splanchnic and pulmonary complications), which can eventually culminate in clinical conditions ranging from portal and pulmonary hypertension to pulmonary, cardiac and renal failure, ascites and encephalopathy. Liver diseases can affect cardiovascular function during the early stages of disease progression. The development of cardiovascular diseases in patients with chronic liver failure is associated with increased morbidity and mortality, and cardiovascular complications can in turn affect liver function and liver disease progression. Furthermore, numerous infectious, inflammatory, metabolic and genetic diseases, as well as alcohol abuse can also influence both hepatic and cardiovascular outcomes. In this Review, we highlight how chronic liver diseases and associated cardiovascular effects can influence different organ pathologies. Furthermore, we explore the potential roles of inflammation, oxidative stress, vasoactive mediator imbalance, dysregulated endocannabinoid and autonomic nervous systems and endothelial dysfunction in mediating the complex interplay between the liver and the systemic vasculature that results in the development of the extrahepatic complications of chronic liver disease. The roles of ageing, sex, the gut microbiome and organ transplantation in this complex interplay are also discussed.

Noninvasive imaging assessment of portal hypertension.

Portal hypertension (PH) is a spectrum of complications of chronic liver disease (CLD) and cirrhosis, with manifestations including ascites, gastroesophageal varices, splenomegaly, hypersplenism, hepatic hydrothorax, hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension. PH can vary in severity and is diagnosed via invasive hepatic venous pressure gradient measurement (HVPG), which is considered the reference standard. Accurate diagnosis of PH and assessment of severity are highly relevant as patients with clinically significant portal hypertension (CSPH) are at higher risk for developing acute variceal bleeding and mortality. In this review, we discuss current and upcoming noninvasive imaging methods for diagnosis and assessment of severity of PH.

Acquired hepatocerebral degeneration and hepatic encephalopathy: one or two entities?

Acquired hepatocerebral degeneration (AHD) and hepatic encephalopathy (HE) are neurological complications of chronic liver disease (CLD) with portosystemic shunt. While HE is common, AHD is a rare entity, and the clinical imaging relationships observed in small series lack validation in large patient cohorts. The aim of this study was to characterize a cohort of AHD patients and to explore possible associations with HE coexistence. We performed a retrospective analysis of patients with a working AHD diagnosis, between 2008 and 2019. Clinical, laboratory, imaging and neuropsychological results at first neurological observation were reviewed and compared between the 'AHD' group and the 'AHD with HE' group. A total of 76 patients were recruited. The most frequent neurological manifestations were neuropsychiatric (93.4%) and extrapyramidal (84.2%). Only 38% of patients had hypermanganesemia. Compared with the AHD group, the AHD with HE group had more hyperkinetic movement disorders (71.4% vs. 38.5%; P=0.05), a higher number of patients on the dementia spectrum (57.7% vs. 20%; P=0.04), higher median ammonia levels (P=0.014) and more widespread cortico-subcortical and pyramidal involvement on brain magnetic resonance imaging. Nineteen patients underwent liver transplantation, with significantly improved survival (P=0.006). Hepatic encephalopathy and AHD often coexist in the same patient. Seventy-six patients with CLD and AHD were evaluated, making this one of the largest reported AHD cohorts. Blood manganese level was a weak diagnostic marker in AHD. Early liver function restoration through liver transplantation improved survival. Our report provides a detailed description of the phenotype and long-term outcome of AHD, with relevance for diagnosis and treatment.

Innovative strategies for reducing the burden of chronic liver disease

Alcohol consumption is increasing in the UK, bringing an increased incidence of cirrhosis, which in turn can lead to hepatic encephalopathy. This complication of cirrhosis can be devastating for patients and their families, and incurs a large health economic burden to the NHS. Cirrhosis is, of course, preventable. As disease prevention is at the heart of the NHS Long Term Plan, it can be used as the basis of a 10-year plan to avoid the complications of chronic liver disease.