Complication Of Chronic Liver Disease Research Articles

Dyspnoea in liver cirrhosis: beyond the ordinary cardiopulmonary cause

BackgroundDyspnoea is a common presentation to the casualties, attributed mostly to cardiopulmonary diseases. Approach to dyspnoea consists of initial acute management to ensure airway patency, respiratory support, and hemodynamic stability, followed by identification of the underlying disease for a definite management to reduce short-term inpatient morbidity and mortality, and rehospitalization in long term. Awareness of the patient’s pre-existing medical conditions is a crucial clue to guide the attending doctor to the primary cause. Dyspnea in chronic liver disease can be due to concomitant cardiopulmonary diseases as well as pulmonary vascular congestion or abnormality associated with portal hypertension such as hepatopulmonary syndrome.Case presentationA 59-year-old man presented with a syncopal attack associated with breathlessness after physical exertion. He had alcohol associated liver cirrhosis for 2 years with a 6-month duration of platypnea and reduced effort tolerance. His physical examination revealed a cyanosed man with normal blood pressure and heart rate, without evidence of systemic and pulmonary fluid congestions. Chest radiography and computed tomography showed no evidence of pulmonary embolism and parenchymal disease and a normal echocardiography ruled out any cardiogenic cause. A diagnosis of hepatopulmonary syndrome was made after the appearance of microbubbles over left atrium at fourth to fifth cardiac cycle demonstrated by a transthoracic contrast-enhanced echocardiography to suggest an extracardiac intrapulmonary shunt.ConclusionsHPS is not an uncommon complication of chronic liver disease. Usual manifestation of HPS is platypnea which needs to be differentiated from orthopnoea associated with cardiopulmonary disease. Nevertheless, there is no effective therapeutic approach of HPS besides liver transplantation.

Global uses of traditional herbs for hepatic diseases and other pharmacological actions: A comprehensive review.

Hepatocellular carcinoma (HCC) is the 7th most common cancer and the 3rd leading cause of cancer-related death worldwide. It is resistant to the majority of chemotherapeutics and has a dismal prognosis. Hepatocellular carcinoma is a prevalent complication of chronic liver disease (CLD) in India. Primary liver cancer is the 6th most common cancer worldwide and the 4th most prevalent cause of cancer-related death. In 2018, it affected 841,000 people and caused 782,000 deaths around the world. Thus, research into the tumor cycle and its prevention through suitable herbal (Unani/Ayurvedic) medication is critical for reducing the impact of primary liver cancer. Treatment options for end-stage liver cancer are limited, necessitating costly liver transplantation, which is unavailable in most countries. Here, we present the results of a comprehensive literature survey to determine the benefits of using various herbs with liver protective and antioxidant properties. This information will be useful to researchers working on liver carcinoma and free radical scavenging, both of which are important in curbing potential carcinogens.

Hepatic Encephalopathy following Transjugular Intrahepatic Portosystemic Shunt Placement.

Hepatic encephalopathy (HE) is a complex condition that arises as a complication of chronic liver disease and portosystemic shunting. Its pathophysiology involves several factors, including impaired ammonia metabolism, portosystemic shunting, sarcopenia, and systemic inflammation. The symptoms of HE can vary significantly, with manifestations ranging from subclinical signs to a comatose state. The West Haven classification system is most commonly used to grade the severity of HE. There is a broad differential for the presenting symptomatology of HE and other causes of altered mental status must be excluded during the workup. HE is a well-known complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. Even though newer stent designs help reduce the risk of HE with smaller diameter shunts, it is essential that patients are counseled regarding this potential risk prior to the procedure. Once a diagnosis of HE has been confirmed, the mainstay of therapy is lactulose and rifaximin. In cases where a patient has received a TIPS placement and continues to experience refractory HE despite medical therapy, it may be necessary to consider shunt reduction or closure.

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Investigation of the influential factors for hepatic osteodystrophy in chronic liver disease: A case-control survey among the patients attending a tertiary care hospital in a rural region of Northern India.

Hepatic osteodystrophy (HOD) is a well-recognized complication of chronic liver diseases (CLD), but the influential factors associated with this complication were studied scarcely in a rural Indian population. The study aims to evaluate the prevalence of HOD and variables that might influence it among cases diagnosed with CLD. It is a cross-sectional observational design survey that was performed in a hospital among the two-hundred cases and controls with a 1:1 ratio who were age (>18 years) and gender matched in a period between April and October 2021. They were subjected to etiological workup, hematological and biochemical investigations, and Vitamin D levels. Then, dual-energy X-ray absorptiometry was used to measure the bone mineral densitometry (BMD) for whole-body, lumbar spine (LS), and hip. HOD was diagnosed according to the WHO criteria. Then, the Chi-square test and conditional logistic regression analysis were used to investigate the influential factors of HOD in CLD patients. The whole-body, LS-spine, and hip BMDs in CLD cases were found to be significantly lower as compared to controls. When the participants among both groups were stratified by age and gender, a significant difference in LS-spine and hip BMD was observed in elderly patients (>60 years), and in both the male and female patients. HOD was found in 70% of CLD patients. After multivariate analysis in CLD patients, we identified that being a male patient (odds ratio [OR] = 3.03), older age (OR = 3.54), duration of illness for more than 5 years (OR = 3.89), decompensated liver dysfunction with Child-Turcotte-Pugh-B and C grading (OR = 8.28), and low level of Vitamin D (OR = 18.45) were the risk factors for HOD. This study concludes that severity of illness and lower level of Vitamin D were the main influential factors for HOD. Supplementation of Vitamin D and calcium in the patients can abate the risk of fractures in our rural communities.

Prevalence of Precipitating Factors of Hepatic Encephalopathy at Nangarhar Regional Hospital

‌Backgroud: Hepatic encephalopathy (HE) or portosystemic encephalopathy (PSE) is a satiuation of disordered in central nervous system’s functions characterrized by the failure of the liver to detoxify noxious substances of gastrointestinal origin due to hepatocellular dysfunction and portosystemic shunting. HE is a complication of chronic liver disease brought on by a number of precipitating circumstances and factors. The aim of this study is to analyze the precipitating factors of HE in cases seen in the Infectious Diseases Ward of Nangarhar Regional Hospital. Materials and Mehtods: A non-interventional hospital based descriptive study was conducted on 50 HE patients in the Infective Ward of Nangarhar Regional Hospital during May 2021 – December 2021. This study also included patients with liver cirrhosis developing HE, known as acute fulminant hepatitis. A comprehensive questionnaire was developed for a better data collection. Detailed clinical history of the patients were taken regarding the present and past diseases. All patients were carefully examined with special attention to anemia, jaundice, asterixes, fever and ascites. Laboratory examinations that recommended for these diseases were also investigated. Results: The results revealed that most of the patients were aged between 40 – 70 years old (82%). The highest frequency of HE disease was recorded in the age of 60-69 (42%). There were four classes of patients according to the classification. Majority of the patients were in fourth class (52%), followed by second class (20%), third class (16%) and first class (12%) of hepatic encephalopathy. It is found that the most crucial exacerbating factors were including infections, constipation and gastrointestinal bleeding. Among them, infections were more frequent which were recorded in 22 patients (44%), followed by constipation in 10 patients (20%) and gastrointestinal bleeding in 6 patient (12%). Among the type of infections the urinary tract infections were accounted for 19% followed by gastrointestinal tract infections (16%) and respiratory tract infections (12%). Conclusion: To determine which precipitating factor is responsible for HE in the eastern region of Afghanistan, frequency of several precipitating factors was examined. Knowing the primary triggering factor makes it simple to develop a plan of action to significantly reduce the incidence of HE. In our investigation, gastrointestinal bleeding, constipations, and infections were the most typical precipitating factors. Due to the fact that hepatitis C is the main and leading cause of liver cirrhosis in Afghanistan.

Updated recommandations for the follow-up of a patient with cirrhosis

A close collaboration between the general practitioner and the gastroenterologist is necessary to optimize the management of a patient with cirrhosis, a frequent and serious complication of chronic liver diseases. Both the treatment of the etiological factor of liver disease and the surveillance of potential complications of cirrhosis are key issues in the proper management of cirrhosis. Preventive measures aim at keeping the patient in a compensated form of cirrhosis which is associated with a better survival. We address here the updated management strategies regarding the most frequent complications of cirrhosis.

Sarcopenia in chronic liver disease, can we predict complications?

Introduction. Sarcopenia is a common complication of chronic liver disease. Today many studies are devoted to sarcopenia impact on the course of liver diseases. At the same time, many studies are being performed on the correlation of sarcopenia in patients with cirrhosis of the liver and the incidence of early complications after liver transplantation. In this regard, we conducted our own retrospective study of the correlation relationship of sarcopenia in patients with chronic liver diseases. Aim. To determine the correlation between the severity of sarcopenia and the incidence of complications of liver cirrhosis in patients on the waiting list for liver transplantation. Material and methods. In our own retrospective observational study, 87 patients suffering from chronic liver diseases and treated at the Minsk Scientific and Practical Center of Surgery, Transplantation and Hematology were included. The assessment of sarcopenia was carried out using the CT technique for assessing indexed parameters of the patient's muscle mass. Mathematical processing was performed using the FDA-approved Osirix TM software. The study was conducted within the framework of the project "ClinicalTrials: NCT04281797" Results. Body mass index was significantly correlated with the presence of sarcopenia (r pb =-0.48, 95% CI [-0.65;-0.27]). At the same time, the groups of patients with and without sarcopenia differed significantly (p<0.0001), (Hedges g=-0.93, 95% CI [-1.37;-0.48]). In groups of patients with various etiological factors of chronic liver diseases, sarcopenia occurred most often among patients with autoimmune hepatitis, while the uneven distribution of the incidence of sarcopenia in different nosological groups was significant (p=0.028;  2 =14.1). Conclusion. Body mass index plays an important prognostic role in muscle mass loss among patients with clinically advanced liver disease. However, skeletal muscle index and Body Mass Index differ significantly between patients with and without sarcopenia. In addition, our study showed a significant difference in the occurrence of sarcopenia in patients on the waiting list of different etiological groups. Thus, further extensive randomized studies in this direction are needed today.

Evaluation of Amino Acids Profile as Non-Invasive Biomarkers of Hepatocellular Carcinoma in Egyptians.

Hepatocellular carcinoma (HCC) is the most dangerous complication of chronic liver disease. It is a multifactorial complicated disease. Hepatitis C and hepatitis B viruses (HCV and HBV, respectively) represent the main causes of HCC in Egypt. Early diagnosis is very important to aid in early intervention. The goal of this research is to evaluate the metabolic role of different amino acids as non-invasive biomarkers over the course of HCC. This study included 302 participants with 97 diagnosed, untreated HCC patients, 81 chronic HCV patients, 56 chronic HBV patients, 18 co-infected patients, and a control group of 50 normal age and gender-matched individuals. All participants provided complete medical histories and underwent complete clinical examinations, abdominal ultrasonography and/or computed tomography, routine laboratory investigations, estimation of serum α-fetoprotein, and determination of amino acid levels using ultra-performance liquid chromatography (UPLC MS/MS). This work revealed a decline in branched chain amino acids (BCAA) and increase in aromatic amino acids (AAA) among infected groups (HCC, HBV, HCV, and co-infected patients) compared to control subjects and a marked change in Fisher's and the BCAAs/tyrosine molar concentration ratios (BTR) between controls and infected groups. Different amino acids could be used as non-invasive markers to discriminate and follow chronic hepatitis patients to predict the course of HCC.

Remote monitoring of cognition in cirrhosis and encephalopathy: future opportunity and challenge.

Hepatic Encephalopathy (HE) is a critically important complication of chronic liver disease and portal hypertension, but especially in early covert stages remains underdiagnosed and a common cause of hospitalization and morbidity. Defined by often subtle neuropsychiatric changes, significant cognitive deficits have been extensively described. While traditional methods of assessment remain underutilized in practice and subject to significant confounding with other diseases, mobile technology has emerged as a potential future tool to provide simple and dynamic cognitive assessments. This review discusses the proliferation of cognitive assessment tools, describing possible applications in encephalopathy and the challenges such an implementation may face. There are significant potential advantages to assessing cognition in real time in order to aid early detection and intervention and provide a more realistic measurement of real-world function. Despite this, there are issues with reliability, privacy, applicability and more which must be addressed prior to wide proliferation and acceptance for clinical use. Regardless, the rapid uptake of mobile technology in healthcare is likely to have significant implications for the future management of encephalopathy and liver disease at large.

РОЛЬ ЭНДОТЕЛИЯ В ФОРМИРОВАНИИ ФИБРОЗА ПЕЧЕНИ

Chronic liver disease is a worldwide health problem. A significant proportion of the manifestations and complications of chronic liver diseases is due to liver fibrosis and its subsequent transition to liver cirrhosis. The initial and the key link in the formation of fibrotic changes in the liver are liver sinusoidal endothelial cells (LSEC). In view of the unique structure and central position of the liver endothelial tissue in the pathogenesis of fibrosis, it seems relevant to present current data in the form of this review. LSECs are the only endothelial cells in the body that lack a basement membrane and contain transcellular pores called fenestrae. At the initial stages of the fibrogenesis process, LSECs change their phenotype: they lose fenestrae and develop a basement membrane, turning into a continuous endothelium. LSECs are involved in fibrosis through the secretion of angiocrine signals that act as paracrine factors that balance the liver’s response to injury towards fibrosis or regeneration. LSEC cells are very sensitive to the slightest changes in the microenvironment, with prolonged exposure they quickly change their phenotype, their numerous functions are disrupted, including vasodilator, anti-inflammatory, antithrombotic and antifibrotic, as well as the regulation of angiogenesis and regeneration, and prevention of HSC activation. Such changes in the phenotype are called endothelial dysfunction. Loss of fenestres (capillaryization) by LSEC cells is the initial event in liver fibrosis. It precedes HSC activation and promotes fibrosis and progression to cirrhosis. Fenestra maintains liver homeostasis, promotes efficient transport of lipoproteins, regulates liver regeneration and immune tolerance. LSEC fenestra are approximately 50-200 nm in diameter, and most of them are clustered into several dozen ultrastructures called sieve plates. Chronic liver injury leads to deep dedifferentiation of LSECs, which lose their vasoprotective properties and become vasoconstrictive, proinflammatory, and prothrombotic. Major molecular dysregulations seen in LSEC in chronic liver disease include fenestra loss and basement membrane development that interfere with the exchange of molecules such as lipoproteins and oxygen with hepatocytes, promoting steatosis and parenchymal apoptosis; reduction of NO by suppression of KLF2 and endothelial NO synthase (eNOS) activity, together with an increase in ROS-mediated NO uptake, leading to activation of hepatic stellate cells and deposition of extracellular matrix; increased production of vasoconstrictors (such as endothelin 1 or thromboxane A2) and pro-inflammatory cytokines, further exacerbating sinusoidal constriction. These pathological changes lead to sinusoidal vasoconstriction, microvascular dysfunction, fibrosis, and ultimately portal hypertension. Thus, LSECs play complex interrelated roles in maintaining liver homeostasis and are involved as factors in inflammation and fibrogenesis in liver diseases. Their unique position, phenotype, and function make them attractive candidates for organ-specific therapies, and it is likely that more therapies targeting these cells will be tested in the future as novel therapies to reduce liver damage and inflammation, and to prevent or reversal of fibrogenesis.

A Study on Correlation of Serum Sodium with the Complications of Chronic Liver Disease

Introduction: Cirrhosis is mostly initiated by alcoholism and hepatitis C, however certainly has many other possible reasons, such as Wilson's disease, hemochromatosis, autoimmune hepatitis, and non-alcoholic fatty disease. Hyponatremia occurs when serum sodium concentration in the blood is less than 135mmol/L, with severe hyponatremia being below 120 mmol/L. In the current study, lower serum sodium levels were associated with improved complications of decompensated chronic liver and mortality leading to the integration of sodium. Aim of the Study: The study aimed to investigate the correlation of serum sodium with the complications of chronic liver disease. Methods: A Prospective cross-sectional study was carried out Department of Gastroenterology and Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shabagh, Dhaka, from March 2014 to February 2015. A total of 100 patients (N=100) for one year were enrolled in this study following the inclusive criteria. Data were collected using the predesigned semi- structured questionnaire. Verbal consent was taken before recruiting the study population. Completed data forms were reviewed, edited, and processed for computer data entry. Result: Among hundred patients (N=100) with decompensated chronic liver disease observe the impact of hyponatremia with the severity of complications. Of them, it was observed that more than one-third of the patients (37,37.0%) belonged to age 31-40 years. The mean age was found 42.2±SD years. It was observed that almost two-thirds of the patients (63,63.0%) were male and thirty-seven (37,37.0%) patients were female. Among the study population, the majority of the patients (90,90.0%) belonged to serum sodium ≤135 mmol/l (Hyponatremia). The mean serum sodium was found 124.7±SD mmol/l. The majority of patients (57,57.0%) had moderate ascites, nineteen patients (19,19.0%) had mild and about one-fourth of the patients (24,24.0%) had severe ascites. In his current analysis, ............

Markers of cell death predict therapy response in patients with cirrhosis and hepatorenal syndrome.

Hepatorenal syndrome is a major complication in patients with cirrhosis and associated with high mortality. Predictive biomarkers for therapy response are largely missing. Cytokeratin18-based cell death markers are significantly elevated in patients with complications of chronic liver disease, but the role of these markers in patients with HRS treated with vasoconstrictors and albumin is unknown. We prospectively analyzed a total of 138 patients with HRS, liver cirrhosis without HRS and acute kidney injury treated at the University Medical Center Mainz between April 2013 and July 2018. Serum levels of M30 and M65 were analyzed by ELISA and clinical data were collected. Predictive ability was assessed by Kaplan-Meier curves, logistic regression and c-statistic. Primary endpoint was response to therapy. M30 and M65 were significantly increased in patients with HRS compared to non-HRS controls (M30: p<0.0001; M65: p<0.0001). Both serum markers showed predictive ability for dialysis- and LTX-free survival but not overall survival. Logistic regression confirmed M30 and M65 as independent prognostic factors for response to therapy. A novel predictive score comprising bilirubin and M65 showed highest predictive ability to predict therapy response. Serum levels of M30 and M65 can robustly discriminate patients into responders and non-responders to terlipressin therapy with a good predictive ability for dialysis- and LTX-free survival in cirrhotic patients. Cell death parameters might possess clinical relevance in patients with liver cirrhosis and HRS.

WAITING LIST FOR LIVER TRANSPLANTATION: CLINICAL AND ECONOMIC BURDEN.

Burden of disease is an indicator that relates to health status. United States 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 $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). 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.

The role of brain inflammation and abnormal brain oxygenhomeostasis in the development of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a frequent complication of chronic liver disease (CLD) and has a complex pathogenesis. Several preclinical and clinical studies have reported the presence of both peripheral and brain inflammation in CLD and their potential impact in the development of HE. Altered brain vascular density and tone, as well as compromised cerebral and systemic blood flow contributing to the development of brain hypoxia, have also been reported in animal models of HE, while a decrease in cerebral metabolic rate of oxygen and cerebral blood flow has consistently been observed in patients with HE. Whilst significant strides in our understanding have been made over the years, evaluating all these mechanistic elements in vivo and showing causal association with development of HE, have been limited through the practical constraints of experimentation. Nonetheless, improvements in non-invasive assessments of different neurophysiological parameters, coupled with techniques to assess changes in inflammatory and metabolic pathways, will help provide more granular insights on these mechanisms. In this special issue we discuss some of the emerging evidence supporting the hypothesis that brain inflammation and abnormal oxygenhomeostasis occur interdependently during CLD and comprise important contributors to the development of HE. This review aims at furnishing evidence for further research in brain inflammation and oxygenhomeostasis as additional therapeutic targets and potentially diagnostic markers for HE.

A mouse model of hepatic encephalopathy: bile duct ligation induces brain ammonia overload, glial cell activation and neuroinflammation

Hepatic encephalopathy (HE) is a common complication of chronic liver disease, characterized by an altered mental state and hyperammonemia. Insight into the brain pathophysiology of HE is limited due to a paucity of well-characterized HE models beyond the rat bile duct ligation (BDL) model. Here, we assess the presence of HE characteristics in the mouse BDL model. We show that BDL in C57Bl/6j mice induces motor dysfunction, progressive liver fibrosis, liver function failure and hyperammonemia, all hallmarks of HE. Swiss mice however fail to replicate the same phenotype, underscoring the importance of careful strain selection. Next, in-depth characterisation of metabolic disturbances in the cerebrospinal fluid of BDL mice shows glutamine accumulation and transient decreases in taurine and choline, indicative of brain ammonia overload. Moreover, mouse BDL induces glial cell dysfunction, namely microglial morphological changes with neuroinflammation and astrocyte reactivity with blood–brain barrier (BBB) disruption. Finally, we identify putative novel mechanisms involved in central HE pathophysiology, like bile acid accumulation and tryptophan–kynurenine pathway alterations. Our study provides the first comprehensive evaluation of a mouse model of HE in chronic liver disease. Additionally, this study further underscores the importance of neuroinflammation in the central effects of chronic liver disease.

Pulmonary vascular disease and exercise hemodynamics in chronic liver disease

Background & aimsPortopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. MethodsWe assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21–24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. ResultsTwo-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50–60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. ConclusionIn chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.

Direct‑acting antiviral treatment decreases serum undercarboxylated osteocalcin in male patients with chronic hepatitis C.

Hepatic osteodystrophy (HOD) is a common complication of chronic liver disease, including viral hepatitis. Hepatitis C virus (HCV) infection is associated with an increased risk of osteoporosis and bone mineral density (BMD) loss. Direct-acting antiviral (DAA) treatment is used to treat HCV infections; however, its effects on bone metabolism have not been reported. We compared the clinical data and bone metabolic markers at the start of DAA treatment and 1 year later in 78 patients. There were 41 female and 37 male patients. HCV was successfully treated with DAA in all patients. Bone metabolic markers included undercarboxylated osteocalcin (ucOC), 25(OH) vitamin D (VD), total type I procollagen N-propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and BMD. BMD was measured in the lumbar spine (mean, L2-L4) and femoral neck using dual-energy X-ray absorptiometry. ucOC in males decreased at 1 year after treatment initiation but not in females. In males, ucOC changes were related to alterations in proteins induced by vitamin K absence-II (PIVKA-II), hemoglobin A1c, and TRACP-5b, which contributed to P1NP and lumbar BMD at the start of DAA. Changes in ucOC among women contributed to the changes in grip strength and TRACP-5b levels. DAA treatment improved ucOC, a useful bone metabolic marker, in HCV-infected male patients. Changes in ucOC contributed to changes in PIVKA-II that likely ameliorated the vitamin K deficiency. DAA treatment has been reported to improve various extrahepatic disorders and abnormal bone metabolism, especially in HOD.

Lenvatinib for the treatment of hepatocellular carcinoma—a real-world multicenter Australian cohort study

IntroductionHepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia.MethodsWe conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes.ResultsA total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59–75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8–14.0) and 5.3 months (95% CI: 2.8–9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child–Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%).ConclusionsLenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Sex is associated with differences in oxidative stress and susceptibility to severe hepatic encephalopathy in bile-duct ligated rats.

Hepatic encephalopathy (HE) is a debilitating neurological complication of chronic liver disease (CLD). Hyperammonemia plays an important role in HE's pathogenesis, acting synergistically with systemic oxidative stress. During CLD, muscle plays a compensatory role in detoxifying ammonia, and therefore muscle loss leads to an increase in the risk of developing HE. With most animal studies involving males, sex's impact on the development of CLD and associated complications such as HE and muscle loss remains unknown. Therefore, we aimed to identify the impact of sex on CLD, HE, and muscle mass loss in a rodent model of CLD. Liver injury markers, hyperammonemia, oxidative stress, muscle mass, and ammonia clearance were measured in female and male bile-duct ligated (BDL) rats. In addition, covert HE was assessed in females while ammonia-precipitated severe HE was assessed in female and male BDL rats, and male BDL rats treated with allopurinol (100 mg/kg), an antioxidant (xanthine oxidase inhibitor). Female BDL developed CLD and HE (impaired motor coordination and night activity) compared to respective SHAM. Hyperammonemia and muscle ammonia clearance were similar between female and male BDL. However, only female BDL rats did not develop muscle loss, brain edema, and short-term memory impairment (vs. female SHAM) and systemic oxidative stress and decreased albumin levels (vs. male BDL). Furthermore, both female BDL and allopurinol-treated male BDL rats were protected against ammonia-induced overt HE. In conclusion, female and male BDL rats develop distinct features of CLD and HE, with systemic oxidative stress playing a pivotal role in the susceptibility to ammonia-precipitated overt HE.