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Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3'-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLg) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases. [ABSTRACT FROM AUTHOR]

Introduction: Leptospirosis is an anthropozoonotic disease. The wide spectrum of clinical manifestations of leptospirosis ranges from mild febrile illness without complications to severe disease with Multiorgan dysfunction. In the central and eastern parts of Uttar Pradesh, India, it is one of the major causes of acute febrile illness. Aim: To determine the seroprevalence, clinical features and geographical distribution of leptospirosis in Central Uttar Pradesh, India. Materials and Methods: This current retrospective observational study was conducted in the Serology Laboratory, Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, India, from January 2022 to December 2022 and data were analysed from January 2023 to March 2023. A total of 625 patients with fever lasting >7 days attending the Outpatient Department (OPD) were included in the study. Serum samples of these patients were tested for Leptospira Immunoglobulin M (IgM) by Enzyme-linked Immunosorbent Assay (ELISA). Clinical, laboratory findings and demographic data were also collected from the hospital software. The patients were also tested for other infectious aetiologies such as malaria, typhoid, dengue and scrub typhus. Data were presented as percentages, and the Odds Ratio (OR), 95% CI, and p-value were used to test the level of significance. Results: Leptospirosis was found to be positive in 63 (10.08%) patients. The patients with leptospirosis belonged to the age group of 21-40 years with a male predominance. The maximum number of cases was from Lucknow district with 23.8% prevalence, followed by Prayagraj (11.11%). The common presenting symptoms were weakness, epigastric pain, myalgia and jaundice. Co-infection with scrub typhus was seen in 11 (17.4%) patients with leptospirosis. None of the other infections showed co-infection with leptospirosis. Coagulopathy and hepatic dysfunction were found in the majority of the patients with leptospirosis. Mortality was seen in five patients with Multiple Organ Dysfunction Syndrome (MODS). Conclusion: The seroprevalence of leptospirosis was found to be 10.08%. To reduce the morbidity and mortality linked to leptospirosis, it is necessary to improve diagnostic skills and the knowledge of physicians for screening the disease in patients with acute febrile illnesses, as it involves multiple systems and has overlapping common presenting symptoms.

The complications of endocrine-metabolic disorders among women of reproductive age, inclusively polycystic ovarian syndrome (PCOS), are cascade of events leading to cardiovascular diseases, as well as non-alcoholic fatty liver disease (NAFLD) which is the leading cause of liver cirrhosis and hepatic carcinoma that often necessitates organ transplant. Paraoxonase-1 (PON-1) has been shown to be protective against metabolic assaults. However, its role in hepatic glucolipid regulation, particularly in PCOS model, has not been documented. Short-chain fatty acid (SCFAs) are essential modulators of metabolic health. The present study hypothesizes that butyrate would ameliorate hepatic dysmetabolism by upregulation of PON-1. Female Wistar rats (8 weeks old) were allotted into groups: control (CTL), butyrate (BUT), letrozole (LET), and LET + BUT. Letrozole (1 mg/kg) was administered for 21 days to induce PCOS. Thereafter, butyrate (200 mg/kg) was administered for 6 weeks. The animals were sacrificed and biochemical assays; histological and immunohistochemical evaluations were performed with appropriate methods. Rats with PCOS showed cystic ovaries, hyperandrogenism, reduced insulin sensitivity, hyperleptinemia, hypoadiponectinemia, dyslipidemia, and hepatic lipid peroxidation/lipotoxicity, as well as increased hepatic caspase-6, proinflammatory markers (NF-kB, SDF-1), decreased antioxidant defense (NrF2), and HIF-1α, with corresponding expression of inflammasome as evaluated immunohistochemically. These alterations were accompanied by a suppressed level of PON-1. However, the administration of butyrate attenuated these hepatic metabolic and cellular perturbations. Results from this study demonstrate that butyrate protects against hepatic glucolipid dysregulation and its comorbid oxidative stress and inflammation in the PCOS model by the modulation of PON-1. [ABSTRACT FROM AUTHOR]

Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3’-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLγ) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases.

The present investigation was executed at Department of Veterinary Medicine and Dr. I. P. Singh Veterinary Clinical Complex and Trauma Centre, College of Veterinary and Animal Sciences, G.B.P.U.A. & T, Pantnagar U.S. Nagar, Uttarakhand, India during the period of September, 2021 to April, 2022. The present study aimed to diagnose hepatic dysfunction in dogs presented to Dr. I.P. Singh Veterinary Clinical Complex and Trauma Centre, Pantnagar. Eighteen dogs presented with varied symptoms of hepatic dysfunction such as fever, anorexia, vomition, emaciation, polydipsia, polyuria, dullness, diarrhoea, icterus and nervous signs indicating hepatic affections were selected irrespective of their age breed, sex and were subjected to haematological, biochemical, radiographic and ultrasonographic examination. Alterations in hematobiochemical parameters of dogs with hepatic dysfunction were compared with healthy dogs. Findings of haematological examination revealed significant decrease in Hb, PCV, TEC, platelets, lymphocytes whereas there was significant increase in neutrophils in dogs with hepatic dysfunction as compared to healthy dogs. Findings of biochemical parameter revealed significant increase in total bilirubin ALT, AST, GGT, ALP whereas there was significant decrease in total protein, albumin, A:G ratio, blood glucose of dogs with hepatic dysfunction as compared to healthy dogs. Radiography and ultrasonography were found useful in diagnosis of canine hepatic dysfunction. Ultrasonography offers additional advantages over radiography by allowing for the evaluation of echogenicity, echotexture, size, shape, and margins of the liver. From the study it was concluded that combination of diagnostic test is reliable to diagnose hepatic dysfunction in dogs and single diagnostic test can be misleading. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia/lymphoma (ATLL) is a rare T-cell lymphoproliferative disease associated with human T-cell leukemia virus type 1. There are four subtypes of ATLL: smoldering, chronic, lymphoma and acute. All subtypes can exhibit extranodal involvement. Hepatic infiltration occurs in the chronic, lymphoma and acute types of ATLL, but symptoms are rare. We report the case of a 32-year-old patient with acute-type ATLL and atypical severe hepatic dysfunction at diagnosis. At first, the patient presented with non-specific signs and symptoms, including severe abdominal pain, jaundice, hepatosplenomegaly, ascites and small lymphadenopathies, as well as leukocytosis, which was initially considered reactive. After excluding acute abdomen, the patient was referred to the hematologist. The diagnosis of acute-type ATLL was unexpectedly suggested by peripheral blood smear and confirmed by immunophenotyping by flow cytometry. Multiple causes of liver dysfunction, including hepatic infiltration, paraneoplastic syndrome, infectious diseases, extrahepatic compression, hemophagocytic syndrome, alcoholic liver disease and drug-induced hepatotoxicity, were taken into account. Considering the concurrence of ATLL diagnosis with liver dysfunction, the favorable clinical and biological evolution after specific hematological treatment, and the absence of imaging supporting other possibilities, we concluded that diffuse hepatic infiltration was the most probable cause. When evaluating hepatic dysfunction, considering a broad differential diagnosis is crucial. While it is uncommon, lymphoma should be included in the list of potential causes. [ABSTRACT FROM AUTHOR]

Approximately 90% of people with diabetes mellitus (DM) are estimated to have type 2 diabetes (T2DM), which causes hepatic dysfunction. Pioglitazone is an antidiabetic medication that ameliorates diabetic liver dysfunction. Rosuvastatin is an antihyperlipidemic drug that alleviates the hepatic damage caused by T2DM. This study's objective was to look into the therapeutic potential of pioglitazone and rosuvastatin in combination in the management of diabetic liver injury induced by a high-fat diet (HFD) and streptozotocin (STZ). Forty male albino rats weighing 150 ± 15 g were used and split into five groups (8 rats in each). Groups II, III, IV, and V undergo induction of T2DM by feeding rats with HFD for 1 month and injecting a low dose of STZ. Group I, however, remained a negative control. Group II was not given any treatment; Group III was treated with pioglitazone; Group IV was treated with rosuvastatin; and Group V was treated with a combination of pioglitazone and rosuvastatin. After 28 days, serum liver enzyme levels and protein profiles were assessed. Expression of the inflammatory cytokines and Cytochrome P2E1 (CYP2E1) genes in the liver was also evaluated. Furthermore, hepatic tissue underwent histopathological examination. The results demonstrated considerable enhancement of the parameters under investigation in groups that were treated with pioglitazone, rosuvastatin alone, or their combination in comparison to the diabetic group. However, the effects of combined therapy are greater than those of monotherapy. In conclusion, concomitant administration of pioglitazone and rosuvastatin had greater potential for attenuating diabetic liver injury than monotherapy. [ABSTRACT FROM AUTHOR]

The liver and thyroid hormones interact at multiple levels to maintain homoeostasis. The liver requires large adequate amounts of thyroid hormones to execute its metabolic functions optimally, and deficiency of thyroid hormones may lead to liver dysfunction. Hypothyroidism has been associated with abnormal lipid metabolism, non-alcoholic fatty liver disease (NAFLD), hypothyroidism-induced myopathy, hypothyroidism-associated gallstones and occasionally, interferon-induced thyroid dysfunction. NAFLD remain an important association with hypothyroidism and further studies are needed that specifically compare the natural course of NAFLD secondary to hypothyroidism and primary NAFLD. Hepatic dysfunction associated with hypothyroidism is usually reverted by normalizing thyroid status. Large scale studies geared towards finding new and effective therapies, especially for NAFLD are needed. The clinician must be aware that there exists overlapping symptomatology between liver dysfunction and severe hypothyroidism which may make delay the diagnosis and treatment of hypothyroidism; this requires a high index of suspicion. [ABSTRACT FROM AUTHOR]

Acute liver failure is an uncommon presentation in the clinic. Common causes for acute liver failure include viral hepatitis and drug-related hepatotoxicity. However, acute liver failure due to Budd-Chiari syndrome is rare. This case highlights the importance of necessary constrast-enhanced imaging studies to rule out vascular etiologies of acute liver failure, in addition to common causes like viral or drug-induced hepatic failure. We present a case of a male Chinese patient who presented with nausea, vomiting, fatigue, and fever after eating a large amount of fatty food. Six days after hospitalization, the patient developed acute liver failure and hepatic encephalopathy. Contrast-enhanced computerized tomography and ultrasound examinations revealed thromboses in the hepatic veins and inferior vena cava. Further testing also showed decreased protein C activity. Therefore, a diagnosis of Budd-Chiari syndrome secondary to protein C deficiency was made. He received supportive care and a transjugular intrahepatic portal shunt. Hepatic function, coagulation panel results, and clinical presentations gradually returned to normal. Budd-Chiari syndrome from protein C deficiency could be a rare but valid cause of acute liver failure in Chinese patients.

Background: Information regarding the safety of entrectinib for previously treated patients and patients with hepatic dysfunction is limited. This is the first case report of treatment modification attributable to hepatic dysfunction caused by crizotinib. Patients: A 76-year-old Japanese woman was referred to the Department of Respiratory Medicine and Allergy after a computed tomography (CT) scan at the time of thyroid surgery. The CT scan revealed an enlarged right upper lobe nodule. After careful examination, she was diagnosed with T3N2M1c stage IV ROS1-positive lung adenocarcinoma; therefore, crizotinib (500 mg/day) was prescribed. On day 861 of treatment, crizotinib was discontinued because of repeatedly observed increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Approximately 2 weeks after crizotinib was discontinued, treatment was restarted with entrectinib 600 mg/day. Conclusions: Entrectinib was prescribed because crizotinib caused hepatic dysfunction; however, the patient experienced grade 3 neutropenia and the creatinine phosphokinase (CPK) levels increased. After the dose reduction, she was able to continue treatment safely, without further worsening of the primary tumor or hepatic dysfunction. Therefore, entrectinib may be an option for patients who need treatment modification because of crizotinib-induced hepatic dysfunction. Increased CPK is a previously unknown adverse event occurring with entrectinib. This information is essential to risk management plans involving this drug. Further information regarding increased CPK and rhabdomyolysis occurring in patients treated with entrectinib is needed.

We presented our observation with dexamethasone (DEX) implant in six eyes of three patients with Vogt–Koyanagi–Harada (VKH) disease who experienced hepatic dysfunction due to the systemic immunosuppressive therapy during their follow-up. Three cases who could not continue with the azathioprine (AZA) or adalimumab (ADA) treatment due to elevated liver enzymes were given consecutive bilateral DEX implant injections during the follow-up. In the first case, oral AZA was discontinued due to an elevation of the liver enzymes at the 2nd month of AZA treatment, and then she received five bilateral DEX implant administrations during the follow-up of 61 months without any intraocular pressure rise or disease recurrence. The remaining two patients had an elevation of the liver enzymes when ADA treatment was added to the prophylactic isoniazid therapy and they each received three bilateral DEX implant administrations within a year again without any complications and disease recurrence. DEX implant can be a safe and effective alternative for individuals with VKH disease whose systemic treatment is ceased due to adverse effects of the systemic treatment and intravitreal therapy with DEX implant can be beneficial to achieve a recurrence-free follow-up. [ABSTRACT FROM AUTHOR]

Background: Scrub Typhus, a Rickettsial disease is an emerging tropical disease mainly in South East Asia. Very few studies are there in pediatric age group and mainly limited to epidemiological and clinical profile only. Aims and Objectives: The main objective of this study is to assess different clinical, laboratory, and biochemical parameters denoting hepatic function in scrub typhus and their role in measuring final outcome and disease severity. Materials and Methods: This observational study included 90 children with history of febrile illness for ≥5 days between 1 and 12 years of age, diagnosed to be a case of scrub typhus by positive IgM ELISA test to assess the hepatic involvement by different clinical, laboratory, and radiological parameters and also to find out their role in disease severity and outcome. Results: Fever followed by vomiting was the most common symptoms with eschar evident in only three patients. Raised aspartate transaminase (AST) and alanine transaminase (ALT) were seen in 71.1% and 64.4%, respectively, with hypoalbuminemia in 78.9%, hepatomegaly in 47.8%, and only 2.2% had altered hepatic echotexture on ultrasonography. All of them had ALT: lactate dehydrogenase (LDH) ratio of

Background: To explore the prognosis and risk factors of postoperative hepatic dysfunction in patients with acute type A aortic dissection. Methods: A total of 156 patients who underwent surgery for acute type A aortic dissection in our hospital from May 2014 to May 2018 were retrospectively enrolled. The patients were divided into 2 groups based on postoperative liver function. The postop-erative model for end-stage liver disease score was used to define hepatic dysfunction. There were 35 patients with postoperative hepatic dysfunction (group hepatic dysfunction, model for end-stage liver disease score ≥ 15) and 121 patients without postoperative hepatic dysfunction (group non-hepatic dysfunction, model for end-stage liver disease score < 15). Univariate and multiple analyses (logistic regression) were used to identify the predictive risk factors. Results: In-hospital mortality rate was 8.3%. Multiple logistic analysis showed that preoperative alanine aminotransferase (P

Abstract Background Hepatitis B virus (HBV) affects the occurrence and survival outcome of various malignant disorders. The study aimed to evaluate the survival outcome of head and neck squamous cell cancer (HNSCC) patients with or without HBV infection. Methods This study included patients with HNSCC who visited Taichung Veterans General Hospital from 2007 to 2015. HBV infection was defined by hepatitis B surface antigen (HBsAg) seropositivity. By propensity score matching, we compared survival outcomes, including progression‐free survival (PFS) and overall survival (OS), among patients with or without HBV infection. Results The prevalence of HBV infection in our cohort was 12.3%. Among the 1,015 patients included in the matched analysis, a higher risk of baseline liver cirrhosis (11.3% vs. 3.4%, p

Abstract Background With the improvement of optimal perioperative drug therapy for breast cancer patients, physicians now have to treat the adverse effects and comorbidities associated with long-term treatments. We report a case who suffered cardiac arrest due to acute myocarditis developed after initiation of adjuvant treatment. Case presentation After completing preoperative chemotherapy and undergoing curative surgery for right breast cancer, a 46-year-old female patient started adjuvant tamoxifen and resumed trastuzumab. Two months later, she complained fever and dyspnea. Blood tests showed a marked increase in hepatic enzymes, and the patient was rushed to our emergency room on suspicion of drug-induced liver injury. In the emergency room, the patient went into cardiac arrest shortly after tachycardia with ST-segment elevation appeared on the monitored electrocardiogram. Resuscitation was started immediately and tracheal intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation were started. Coronary angiography results were negative for ischemic heart disease. A diagnosis of fulminant myocarditis was made and steroid pulse therapy and immunoglobulin therapy were started. After the start of treatment, the symptoms of heart failure improved steadily and the patient was discharged on the 28th day. Histological findings of the myocardial biopsy revealed degeneration and necrosis of myocardial cells with marked lymphocytic infiltration, consistent with the histology of lymphocytic myocarditis. Serum cytomegalovirus, coxsackie B virus and adenovirus antibodies were all elevated and these findings were consistent with acute viral myocarditis. Conclusions We report a case with strong indications for therapy-induced liver damage, who was ultimately diagnosed with acute viral myocarditis and successfully treated with multidisciplinary therapy. We believe that our findings would be useful for other clinicians in managing similar patients.

Diffuse large B‐cell lymphoma (DLBCL) is an aggressive subtype of non‐Hodgkin lymphoma with a high rate of disease relapse despite the achievement of clinical responses to frontline chemoimmunotherapy treatments. Loncastuximab tesirine‐lpyl is a novel anti‐CD19 antibody conjugated to an alkylating pyrrolobenzodiazepine agent (SG3199), and it has been approved for relapsed/refractory (r/r) DLBCL. Baseline moderate to severe hepatic impairment has an unclear impact on the safety of loncastuximab tesirine‐lpyl, and there is a lack of clear guidance on dose adjustment from the manufacturer. The authors present two cases of r/r DLBCL safely treated with full‐dose loncastuximab tesirine‐lpyl in the setting of severe hepatic dysfunction. Baseline moderate to severe hepatic impairment has an unclear impact on the safety of loncastuximab tesirine‐lpyl. Two cases of relapsed/refractory diffuse large B‐cell lymphoma safely treated with full‐dose loncastuximab tesirine‐lpyl in the setting of severe hepatic dysfunction are presented. [ABSTRACT FROM AUTHOR]

Simple Summary: Amanitin-containing mushroom poisonings occur worldwide and affect both humans and animals. Intoxication from these mushrooms can cause severe gastrointestinal, liver, and neurologic dysfunction, which can result in death. This case report discusses amanitin-induced liver dysfunction and the development of hypoadrenocorticism following recovery in a dog. A clearer understanding of post-intoxication outcomes would help veterinarians prepare pet owners to understand the implications and long-term consequences of amanitin intoxication. A 10-year-old, female spayed Labrador Retriever was referred for acute hepatopathy and urinary retention. Blood work from the initial presentation (day 0) revealed a severe, mixed hepatopathy. Over the course of the patient's hospitalization, the patient developed liver insufficiency. Urine was submitted for toxicological screening and revealed detection of a trace concentration of alpha-amanitin. The patient was treated supportively for alpha-amanitin intoxication and was discharged from the hospital on day 8, with most biochemical parameters being markedly improved. The patient was persistently hyporexic at the time of discharge. On day 15, at a recheck appointment, the patient had lost 2.4 kg and liver enzymology revealed improved values. On day 24, the patient was presented for anorexia and vomiting and had lost another 2.3 kg. Blood work and endocrinological testing at that time were consistent with hypoadrenocorticism. The patient was started on glucocorticoids and mineralocorticoids. At day 106, the patient was doing well clinically while receiving monthly mineralocorticoids and daily glucocorticoids. This case report is the first to describe the chronological association between alpha-amanitin-induced liver dysfunction and the subsequent development of adrenal insufficiency in a dog. [ABSTRACT FROM AUTHOR]

Background: DENV (dengue viral infection) is a non-hepatotropic RNA virus, but hepatic involvement is common. High level of viremia is associated with involvement liver and other organs. Present study is a prospective study which is aimed to know about the, pattern of hepatic involvement in dengue patients. Methods: This is a prospective hospital-based study conducted in the Department of General Medicine of tertiary care hospital of central India. During study period 200 clinically and serologically positive patients of Dengue fever, Dengue haemorrhagic fever and Dengue shock syndrome, classified as per the, definition of national vector borne disease control programme Govt. of India. Results: The mean value of total bilirubin was found to be 0.8 mg/dl in patients with dengue fever (DF), 0.96 mg/dl in patients with dengue hemorrhagic fever (DHF), and 1.08 mg/dl in patients with dengue shock syndrome (DSS). The mean value of aspartate aminotransferase (AST) was 77.44 IU/L in the dengue fever (DF) group, 112.32 IU/L in the dengue hemorrhagic fever (DHF) group, and 486.28 IU/L in the dengue shock syndrome (DSS) group. The average alanine aminotransferase (ALT) level in the DF group was 94.36 IU/L, while in the DHF group it was 386.42 IU/L. The average serum albumin levels were found to be 3.97 gm/dl in the DF group, 3.65 gm/dl in the DHF group, and 3.49 gm/dl in the DSS group. The average serum globulin levels were 2.98 mg/dl in the DF group, 2.86 gm/dl in the DHF group, and 2.69 gm/dl in the DSS group. The serum alkaline phosphate level exhibited an elevation in all groups under investigation. The mean value of ALP was found to be 118.46 IU/L in the DF group, 164.32 IU/L in the DHF group, and 342.42 IU/L in the DSS group. Conclusion: The pattern of hepatic involvement of liver in dengue fever varies as per the severity of disease. In milder case of dengue fever liver function test was normal but there was hepatomegaly was present commonly but in severe form of disease pattern of hepatic involvement varies from tender hepatomegaly to significant increase in liver enzyme. [ABSTRACT FROM AUTHOR]

We presented our observation with dexamethasone (DEX) implant in six eyes of three patients with Vogt–Koyanagi–Harada (VKH) disease who experienced hepatic dysfunction due to the systemic immunosuppressive therapy during their follow-up. Three cases who could not continue with the azathioprine (AZA) or adalimumab (ADA) treatment due to elevated liver enzymes were given consecutive bilateral DEX implant injections during the follow-up. In the first case, oral AZA was discontinued due to an elevation of the liver enzymes at the 2nd month of AZA treatment, and then she received five bilateral DEX implant administrations during the follow-up of 61 months without any intraocular pressure rise or disease recurrence. The remaining two patients had an elevation of the liver enzymes when ADA treatment was added to the prophylactic isoniazid therapy and they each received three bilateral DEX implant administrations within a year again without any complications and disease recurrence. DEX implant can be a safe and effective alternative for individuals with VKH disease whose systemic treatment is ceased due to adverse effects of the systemic treatment and intravitreal therapy with DEX implant can be beneficial to achieve a recurrence-free follow-up.

Xuezhou Cai,1,2,* Wei Li,1,* Jian Yang,1,3,* Guangjie Wu,1 Jianxin Song,4 Xuepeng Gong,1 Dong Liu,1 Yan He1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pharmacy, Xianning Central Hospital, Hubei University of Science and Technology, Xianning, People’s Republic of China; 3Department of Pharmacy, General Hospital of Central Theater Command of Chinese People’s Liberation Army, Wuhan, People’s Republic of China; 4Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan He; Dong Liu, Email heyan_may@hotmail.com; ld2069@outlook.comBackground: There is a wide debate about the efficacy and safety of voriconazole in patients with impaired hepatic function at Child-Pugh C level.Objective: The purpose of this study was to investigate the safety and efficacy between the two groups treated with different dosages of voriconazole (400mg/day vs 200mg/day) in the treatment of invasive fungal infections (IFIs) in patients with hepatic dysfunction.Methods: A retrospective study enrolling patients with hepatic dysfunction receiving intravenous voriconazole for IFIs from January 1st, 2017, to December 30th, 2021 was conducted. Patients were enrolled in the 400mg per day dose group and 200mg per day dose group. In patients with the same degree of hepatic impairment, factors affecting prognosis were screened and differences in steady-state blood trough concentrations (Cmin) of voriconazole, positive G/GM tests and adverse effects (AEs) were compared between the two groups described above.Results: In total, 308 patients with IFIs were enrolled. For Child-Pugh C class, patients receiving the halved maintenance dose had a lower Cmin and AEs rate but higher recovered rate compared to those receiving maintenance dose, and significant predictors of recovery were dosage (OR, 5.131; 95% CI, 1.599– 16.464; p = 0.006) and diabetes (OR, 0.111; 95% CI, 0.020– 0.597; p = 0.010). For patients of Child-Pugh A & B class, chronic liver disease (OR, 0.334; 95% CI, 0.159– 0.704; p = 0.004) was a prognosis-related factor.Conclusion: Halving maintenance dose ensure the efficacy and safety of voriconazole in patients suffering from invasive fungal infections with serious hepatic dysfunction.Keywords: hepatic dysfunction, invasive fungal infections, voriconazole, through concentration, Child-Pugh

Aim:Overall, around 14-18% of non-acquired immunodeficiency syndrome-related deaths are due to liver disease in human immunodeficiency virus (HIV) patients. With a prevalence of 15%, cirrhosis appears to be a more serious consequence. There are many non-invasive markers for assessing liver fibrosis but their utility in pediatric HIV patients has not been explored.Materials and Methods:To assess the occurrence of liver dysfunction and the levels of combination biomarkers of liver dysfunction [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index] in HIV positive children. A total of 44 HIV positive children aged

Purpose: In our previous study, we showed that Lycium chinense Miller fruit extract (LFE) exerted hepatoprotective effects in mice. In the current study, we examined the effect of LFE on liver enzyme levels in subjects with mild hepatic dysfunction. Methods: A total of 90 subjects, aged 19 to 70 years old, with abnormal alanine aminotransferase (ALT) levels, were randomly placed into either an LFE (n = 45) treatment group or a placebo group (n = 45). During the 12-week clinical trial, subjects in each group received either LFE or placebo capsules, and were instructed to take four tablets per day (1760 mg/day). The primary outcome of the study was the changes of ALT and γ-glutamyltransferase (GGT) levels in each subject. The safety of LFE supplementation was assessed and adverse events were recorded. Results: LFE supplementation for 12 weeks resulted in a significant reduction of ALT (P = 0.0498) and GGT (P = 0.0368) levels in comparison to the placebo. No clinically significant changes were observed in any safety parameters. Conclusion: These results suggest that LFE can be applied to subjects with mild hepatic dysfunction with no possible side effects. Trial registration: This study was registered at the Clinical Research Information Service (CRIS) as no. KCT0003985. [ABSTRACT FROM AUTHOR]

Background: Scrub Typhus, a Rickettsial disease is an emerging tropical disease mainly in South East Asia. Very few studies are there in pediatric age group and mainly limited to epidemiological and clinical profile only. Aims and Objectives: The main objective of this study is to assess different clinical, laboratory, and biochemical parameters denoting hepatic function in scrub typhus and their role in measuring final outcome and disease severity. Materials and Methods: This observational study included 90 children with history of febrile illness for =5 days between 1 and 12 years of age, diagnosed to be a case of scrub typhus by positive IgM ELISA test to assess the hepatic involvement by different clinical, laboratory, and radiological parameters and also to find out their role in disease severity and outcome. Results: Fever followed by vomiting was the most common symptoms with eschar evident in only three patients. Raised aspartate transaminase (AST) and alanine transaminase (ALT) were seen in 71.1% and 64.4%, respectively, with hypoalbuminemia in 78.9%, hepatomegaly in 47.8%, and only 2.2% had altered hepatic echotexture on ultrasonography. All of them had ALT: lactate dehydrogenase (LDH) ratio of <5. Shock was the most important predictor of duration of hospital stay whereas serum AST was an important predictor for final outcome and duration of hospital stay. Conclusion: Predominant feature of hepatic involvement in scrub typhus resembles that of anicteric hepatitis. Serum ALT: LDH ratio may be an important indicator of scrub hepatitis. Among lab parameters serum AST is the most important predictor of disease mortality and morbidity. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) are ubiquitous in aquatic and terrestrial ecosystem, increasingly becoming a serious concern of human health. Many studies have explored the biological effects of MPs on animal and plant life in recent years. However, information regarding the effects of MPs on aging and lifespan is completely lacking in vertebrate species to date. Here we first confirm the bioavailability of MPs by oral delivery in the annual fish N. guentheri. We then show for the first time that administration of MPs not only shortens the lifespan but also accelerates the development of age-related biomarkers in N. guentheri. We also demonstrate that administration of MPs induces oxidative stress, suppresses antioxidant enzymes, reduces digestive enzymes, and causes hepatic dysfunction. Therefore, we propose that administration of MPs reduces lifespan of N. guentheri via induction of both suppressed antioxidant system and digestive disturbance as well as hepatic damage. Our results also suggest that smaller MPs appear more toxic to digestion, metabolism and growth of animals. [ABSTRACT FROM AUTHOR]

Background: With the improvement of optimal perioperative drug therapy for breast cancer patients, physicians now have to treat the adverse effects and comorbidities associated with long-term treatments. We report a case who suffered cardiac arrest due to acute myocarditis developed after initiation of adjuvant treatment. Case presentation: After completing preoperative chemotherapy and undergoing curative surgery for right breast cancer, a 46-year-old female patient started adjuvant tamoxifen and resumed trastuzumab. Two months later, she complained fever and dyspnea. Blood tests showed a marked increase in hepatic enzymes, and the patient was rushed to our emergency room on suspicion of drug-induced liver injury. In the emergency room, the patient went into cardiac arrest shortly after tachycardia with ST-segment elevation appeared on the monitored electrocardiogram. Resuscitation was started immediately and tracheal intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation were started. Coronary angiography results were negative for ischemic heart disease. A diagnosis of fulminant myocarditis was made and steroid pulse therapy and immunoglobulin therapy were started. After the start of treatment, the symptoms of heart failure improved steadily and the patient was discharged on the 28th day. Histological findings of the myocardial biopsy revealed degeneration and necrosis of myocardial cells with marked lymphocytic infiltration, consistent with the histology of lymphocytic myocarditis. Serum cytomegalovirus, coxsackie B virus and adenovirus antibodies were all elevated and these findings were consistent with acute viral myocarditis. Conclusions: We report a case with strong indications for therapy-induced liver damage, who was ultimately diagnosed with acute viral myocarditis and successfully treated with multidisciplinary therapy. We believe that our findings would be useful for other clinicians in managing similar patients. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) affects the occurrence and survival outcome of various malignant disorders. The study aimed to evaluate the survival outcome of head and neck squamous cell cancer (HNSCC) patients with or without HBV infection. Methods: This study included patients with HNSCC who visited Taichung Veterans General Hospital from 2007 to 2015. HBV infection was defined by hepatitis B surface antigen (HBsAg) seropositivity. By propensity score matching, we compared survival outcomes, including progression‐free survival (PFS) and overall survival (OS), among patients with or without HBV infection. Results: The prevalence of HBV infection in our cohort was 12.3%. Among the 1,015 patients included in the matched analysis, a higher risk of baseline liver cirrhosis (11.3% vs. 3.4%, p < 0.001) and initial hepatic dysfunction (10.8% vs. 5.4%, p = 0.005) rates were observed than those without HBV infection at baseline. The 5‐year OS was 43.1% and 53.2% (p < 0.001) and the 5‐year PFS was 37.4% and 42.3% (p = 0.007) in patients with and without HBV infection, respectively. The incidence of subsequent hepatic dysfunction showed no difference between patients with and without HBV infection (29.6% vs. 26.8%, p = 0.439). Conclusions: Patients with HNSCC and HBV infection were younger and had a higher risk of cirrhosis compared to those without HBV infection. Moreover, HBV infection significantly influenced the OS and PFS outcomes but not subsequent hepatic dysfunction in patients with HNSCC. [ABSTRACT FROM AUTHOR]

Aim: Overall, around 14-18% of non-acquired immunodeficiency syndrome-related deaths are due to liver disease in human immunodeficiency virus (HIV) patients. With a prevalence of 15%, cirrhosis appears to be a more serious consequence. There are many non-invasive markers for assessing liver fibrosis but their utility in pediatric HIV patients has not been explored. Materials and Methods: To assess the occurrence of liver dysfunction and the levels of combination biomarkers of liver dysfunction [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index] in HIV positive children. A total of 44 HIV positive children aged <15 years attending the antiretroviral therapy (ART) clinic were enrolled and evaluated for liver dysfunction using non-invasive biomarkers and ultrasonography (USG) scoring. Results: Deranged biomarkers-AST/ALT ratios, APRI scores, and FIB-4 index were found in 95%, 6.8%, and 4.5% children respectively. 7% of children showed moderate to severe liver fibrosis on USG scoring. Also, anemia, nevirapine in ART regimen, longer ART duration, immunosuppression, and lower body mass index values were found as risk factors associated with deranged biomarkers. Conclusion: Hepatic dysfunction is reflected by deranged AST/ALT ratios among HIV-positive children in this study. Further, the elevated APRI scores and FIB-4 index in some cases signal evolving liver fibrosis. [ABSTRACT FROM AUTHOR]

No clear consensus has been reached about the clinical features in hepatitis B virus (HBV)-associated non-Hodgkin's lymphoma (NHL) patients. We performed a systematic review and meta-analysis to explore the clinical characteristics and prognosis of NHL patients with chronic HBV infection (HBsAg+). Seven electronic databases were searched for relevant studies up to 31 January 2021. Hazard ratio (HR) or odds ratio (OR) corresponding to 95% confidence interval (CI) were calculated to estimate the outcomes. The primary outcome was survival outcome, including overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed in diffuse large B-cell lymphoma (DLBCL) patients. Twenty-three retrospective studies, comprising of 1202 HBsAg+ NHL patients and 4448 HBsAg− NHL patients, were included. Twenty-two studies were conducted on Chinese patients. Compared with HBsAg− NHL patients, significantly shorter OS (HR 1.68; 95% CI 1.48–1.91) and PFS (HR 1.80; 95% CI 1.20–2.71), lower rate of complete remission (OR 0.59, 95% CI 0.44–0.80) and higher frequency of hepatic dysfunction during chemotherapy (OR 3.46; 95% CI 2.61–4.57) were demonstrated in HBsAg+ NHL patients. Moreover, HBsAg+ patients were characterized by a younger age of disease onset, advanced disease stage, higher level of LDH and more frequent presence of B symptoms, and involvement of spleen and liver at diagnosis. Furthermore, subgroup analysis in DLBCL patients was also showed similar results. Our study implicated that NHL patients, especially DLBCL, with chronic HBV infection displayed inferior prognosis, higher incidence of hepatic dysfunction during chemotherapy and distinct clinical features. [ABSTRACT FROM AUTHOR]

Abstract Stauffer syndrome, first described by Herbert Stauffer in 1961, is a hepatic paraneoplastic syndrome characterized by multiple extrahepatic malignancies, most commonly renal cell carcinoma. The syndrome manifests a wide range of symptoms caused by various pathophysiological mechanisms and presents with abnormalities in liver function tests in either cholestatic or non-cholestatic patterns. Stauffer’s syndrome is classified into two types: classical and jaundice variants. Some crossovers continue to occur, complicating the diagnosis of such a rare and frequently missed syndrome, which can be the only diagnostic clue for the retrograde detection of a hidden malignancy. To bridge the gap regarding such an important, but still unrecognized, syndrome, not only did we thoroughly cover what had previously been proposed in the literature, but we also proposed a diagnostic protocol based on multicenter experience with such a rare disease.

Summary: Objectives: The biological membranes are important for cell structure and function but, during diseased conditions such as diabetes and in chronic alcoholism, they may be impaired. Nitroxidative stress mediated by persistent hyperglycemia is a major complication in diabetics with alcohol abuse. The present study is intended to investigate the antioxidant, anti-diabetic, and hepatoprotective effects of aqueous green tea extract (GTE) against cumulative effects of alcohol and diabetic pathology, focusing liver mitochondrial membranes. Methods: Mitochondrial membrane fluidity and membrane Na+/K+ and Mg2+ATPases were measured. Displacement loop (D-loop) of mitochondrial DNA (mt-DNA) was screened by PCR-Sanger's sequencing method. In addition, nuclear and mitochondrial encoded genes were analyzed. Molecular docking studies were performed to screen potential targets using the docking module implemented in Pyrx2010. Results: In the present study, marked mitochondrial-DNA deletions were observed in diabetic-alcohol group which were ameliorated by GTE treatment. Also, GTE restored the alterations in the exacerbated levels of membrane fluidity and activities of Na+/K+ and Mg2+ ATPase to normalcy. ADME properties were evaluated for the ligand, Epigallocatechin 3 Gallate (EGCG) and reference drug, Rosiglitazone (RTG). It showed that, higher binding affinities and energy profiles of EGCG with the active site ofinducible nitric oxide synthase (iNOS) compared to RTG making non-bonded interactions with their active residues and surrounding allosteric residues. Discussion: The present investigation demonstrated that, EGCG would be a promising next generation anti-diabetic compound as well as anti-inflammatory drug, and may be effectively used in the treatment of hepatopathy induced by double jeopardy of diabetes and alcohol abuse.

Alcoholic liver disease (ALD) is a major cause of chronic liver injury characterized by steatosis, inflammation, and fibrosis. This study explored the hepatoprotective mechanisms of alpha-asarone in a mouse model of chronic-binge alcohol feeding. Adult male mice were randomized into control, alcohol, and alcohol plus alpha-asarone groups. Serum aminotransferases and histopathology assessed liver injury. Oxidative stress was evaluated via malondialdehyde content, glutathione, superoxide dismutase, and catalase activities. Pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified by ELISA. P53-mediated apoptosis was determined by immunohistochemistry. Key autophagy markers phospho-AMPK, AMPK, Beclin-1, LC3-I/LC3-II ratio, and LC3 were examined by immunoblotting. Alcohol administration increased serum ALT, AST and ALP, indicating hepatocellular damage. This liver dysfunction was associated with increased oxidative stress, inflammation, p53 expression and altered autophagy. Alpha-asarone treatment significantly decreased ALT, AST and ALP levels and improved histological architecture versus alcohol alone. Alpha-asarone also mitigated oxidative stress, reduced TNF-α, IL-1β and IL-6 levels, ameliorated p53 overexpression and favorably modulated autophagy markers. Our findings demonstrate that alpha-asarone confers protective effects against ALD by enhancing antioxidant defenses, suppressing hepatic inflammation, regulating apoptotic signaling, and restoring autophagic flux. This preclinical study provides compelling evidence for the therapeutic potential of alpha-asarone in attenuating alcohol-induced liver injury and warrants further evaluation as a pharmacotherapy for ALD. [Display omitted] • Alpha-asarone improved liver function; decreased ALT, AST, ALP. • Reduced liver oxidative stress: increased GSH, SOD, CAT; decreased MDA. • Lowered inflammation: suppressed TNF-α, IL-1, IL-6. • Modulated autophagy: increased AMPK; decreased Beclin-1, LC3. • Alleviated apoptosis: reduced p53, protecting against alcohol damage. [ABSTRACT FROM AUTHOR]

Abstract Background Trametinib is an oral MEK 1/2 inhibitor, with a single agent recommended phase 2 dose (RP2D) of 2 mg daily (QD). This study was designed to evaluate RP2D, maximum tolerated dose (MTD), and pharmacokinetic (PK) profile of trametinib in patients with advanced solid tumors who had various degrees of hepatic dysfunction (HD). Methods Advanced cancer patients were stratified into 4 HD groups based on Organ Dysfunction Working Group hepatic function stratification criteria: normal (Norm), mild (Mild), moderate (Mod), severe (Sev). Dose escalation was based on “3 + 3” design within each HD group. PK samples were collected at cycle 1 days 15-16. Results Forty-six patients were enrolled with 44 evaluable for safety [Norm=17, Mild=7, Mod (1.5 mg)=4, Mod (2 mg)=5, Sev (1 mg)=9, Sev (1.5 mg)=2] and 22 for PK analysis. Treatment related adverse events were consistent with prior trametinib studies. No treatment related deaths occurred. Dose limiting toxicities (DLTs) were evaluable in 15 patients (Mild=6, Mod (1.5 mg)=3, Mod (2 mg)=2, Sev (1 mg)=3 and Sev (1.5 mg)=1). One DLT (grade 3 acneiform rash) was observed in a Sev patient (1.5 mg). Dose interruptions or reductions due to treatment related adverse events occurred in 15 patients (34%) [Norm=9, 53%; Mild=2, 29%; Mod (1.5 mg)=1, 33%; Mod (2 mg)=2, 33%; Sev (1 mg)=1, 11%; Sev (1.5 mg)=1; 50%]. There were no significant differences across HD groups for all PK parameters when trametinib was normalized to 2 mg. However, only limited PK data were available for the Mod (n = 3) and Sev (n = 3) groups compared to Norm (n = 10) and Mild (n = 6) groups. Trametinib is heavily protein bound, with no correlation between serum albumin level and unbound trametinib fraction (p = 0.26). Conclusions RP2D for trametinib in Mild HD patients is 2 mg QD. There are insufficient number of evaluable patients due to difficulty of patient accrual to declare RP2D and MTD for Mod and Sev HD groups. DLTs were not observed in the highest dose cohorts that reached three evaluable patients – 1.5 mg QD in Mod group, and 1 mg QD in Sev group. Trial registration This study was registered in the ClinicalTrials.gov website ( NCT 02070549 ) on February 25, 2014. .

Introduction/Objective. Colorectal cancer (CRC) is currently the third most common cancer in incidence in the United States and accounts for about 8.5% of all cancer related deaths. Our study aim was to determine the parameters that contribute to the survival of CRC patients with hepatic dysfunction, attention to the positive effects on survival when the most appropriate clinical approaches. Methods.Patients with CRC, diagnosed with hepatic dysfunction, and who were followed up in our inpatient service in the last two years were included in our study. Survival rates were analyzed starting from after the development of hepatic failure. Results. A total of 57 patients were included in the study, 44 (77.2%) were colon carcinoma, and 13 (22.8%) were rectal carcinoma patients, and 14 (24.56%) were female. Bile duct dilatation (BD) was detected in 19 (33%) of 57 patients with imaging methods. The median OS was calculated as 4 vs. 1.4 months in patients with BD compared to patients without BD (p < 0.001). Survival times were significantly higher in patients with BD compared to those without dilatation, and in patients without renal failure compared to those with renal failure. Conclusion. In cancer patients with hepatic dysfunction, those with additional renal failure had shorter survival times and a worse prognosis. The longer survival of patients with BD was attributed to the optimal timing of the percutaneous transhepatic cholangiography insertion, close clinical and inflammation marker follow-ups, and early prevention of external biliary drainage, therefore preventing a possible septic complication early on.

Objectives No clear consensus has been reached about the clinical features in hepatitis B virus (HBV)-associated non-Hodgkin’s lymphoma (NHL) patients. We performed a systematic review and meta-analysis to explore the clinical characteristics and prognosis of NHL patients with chronic HBV infection (HBsAg+). Methods Seven electronic databases were searched for relevant studies up to 31 January 2021. Hazard ratio (HR) or odds ratio (OR) corresponding to 95% confidence interval (CI) were calculated to estimate the outcomes. The primary outcome was survival outcome, including overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed in diffuse large B-cell lymphoma (DLBCL) patients. Results Twenty-three retrospective studies, comprising of 1202 HBsAg+ NHL patients and 4448 HBsAg− NHL patients, were included. Twenty-two studies were conducted on Chinese patients. Compared with HBsAg− NHL patients, significantly shorter OS (HR 1.68; 95% CI 1.48–1.91) and PFS (HR 1.80; 95% CI 1.20–2.71), lower rate of complete remission (OR 0.59, 95% CI 0.44–0.80) and higher frequency of hepatic dysfunction during chemotherapy (OR 3.46; 95% CI 2.61–4.57) were demonstrated in HBsAg+ NHL patients. Moreover, HBsAg+ patients were characterized by a younger age of disease onset, advanced disease stage, higher level of LDH and more frequent presence of B symptoms, and involvement of spleen and liver at diagnosis. Furthermore, subgroup analysis in DLBCL patients was also showed similar results. Conclusion Our study implicated that NHL patients, especially DLBCL, with chronic HBV infection displayed inferior prognosis, higher incidence of hepatic dysfunction during chemotherapy and distinct clinical features.

Summary: Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft‐versus‐host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1‐year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1‐year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Dengue fever is one of the most common vectorborne infections worldwide and is now endemic in Kerala. Knowledge about changing clinical presentation of dengue fever is important for timely diagnosis and appropriate management. Aim: To document changing trends in clinical presentation and course of illness among patients admitted with dengue fever in Kerala, India. Materials and Methods: This hospital-based, retrospective, observational study was conducted at Government Medical College and Hospital, Kannur, Kerala, India, from September 2021 to June 2022. The patients with dengue fever, presented in seasonal epidemic of the year 2019 was compared to similar patients presented during the year 2014. Data regarding clinical presentation, duration of hospital stay, complications and haematological parameters of the study population was collected using prevalidated questionnaire. Descriptive data were expressed in frequency, percentage, mean and standard deviation. Continuous and discrete variables were compared by Welch's t-test, whereas categorical variables were compared using Pearson's Chi-square test. Results: Out of the total 184 patients studied, 91 were from 2014 and 93 from 2019. The major presenting complaints were fever, body aches, headache, nausea and vomiting, arthralgia, and retroorbital pain incidence of which were similar in both the study years. Patients admitted in 2019 have shorter duration of fever (5.78 vs 6.79 days), earlier onset of severe thrombocytopaenia (6.62 vs 7.27 days) and delayed onset of complications (5.56 vs 3.6 days) compared to those admitted in 2014. They also had higher incidence of thrombocytopaenia (70.97% vs 54.94%) and complications (49.46% vs 14.29%) during the course of their illness. Conclusion: The study indicates towards a significant shift in clinical presentation of dengue fever in Kerala which may influence the admission and monitoring protocol of dengue fever patients in the years to come. [ABSTRACT FROM AUTHOR]

Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are unclear. Method: We assessed the hepatic function by using the dynamic LiMAx® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb® in a prospective, observational study. Points of measurement: T1: diagnosis of sepsis or septic shock; T2 and T3: 24 h and 48 h after the start of CytoSorb®; T4: 24 h after termination of CytoSorb®. Results: The hepatic biotransformation capacity measured by LiMAx® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb®, a significant improvement in LiMAx® values appeared from T3 to T4. This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range. Conclusions: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx® in ventilated ICU patients under CytoSorb®. Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction. Discussion: Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver. Conclusion: During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Liver fibrosis staging is a key element driving the prognosis of patients with chronic liver disease. Currently, biopsy is the only technique capable of diagnosing liver fibrosis in patients with alcohol‐related liver disease (ArLD) and nonalcoholic fatty liver disease (NAFLD) unequivocally. Noninvasive (e.g. plasma‐based) biomarker assays are attractive tools to diagnose and stage disease, yet must prove that they are reliable and sensitive to be used clinically. Here, we demonstrate proton nuclear magnetic resonance as a method to rapidly quantify the endogenous concentration of ammonium ions from human plasma extracts and show their ability to report upon early and advanced stages of ArLD and NAFLD. We show that, irrespective of the disease etiology, ammonium concentration is a more robust and informative marker of fibrosis stage than current clinically assessed blood hepatic biomarkers. Subject to validation in larger cohorts, the study indicates that the method can provide accurate and rapid staging of ArLD and NAFLD without the need for an invasive biopsy. [ABSTRACT FROM AUTHOR]

Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded. Responses were aggregated and reported in a comparative fashion. Screening for portal hypertension (PH) was routinely performed in 54% centers, never in 12% and guided by clinical manifestations in the remaining. Involvement of hepatologists/gastroenterologists was always/very often considered in patients with signs of PH prior to transplant. Centers reported that radiological evidence of PH did not routinely represent a formal contraindication for allo-HCT in most cases (78%). Of note, most centers (61%) did not perform routine screening for gastroesophageal varices; this was systematically considered or guided by clinical manifestations in only 7% and 32% centers, respectively. Presence of gastroesophageal varices was always (15%) or occasionally (19%) considered a formal contraindication to allo-HCT. A prior history of portal vein thrombosis never (78%) or occasionally (15%) represented a formal contraindication. Three Centers would not proceed to transplant in such cases. Less importance was assigned to non-portal splanchnic vein thrombosis (SVT), with all but one centre proceeding to transplant regardless of prior SVT. This survey highlights a considerable heterogeneity across responding centers in approaching MF-related comorbidities prior to transplant, suggesting that harmonisation guidelines are needed to address these issues in this patient population., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Abstract Background Hepatic dysfunction (HD) increases the morbidity and mortality rates after cardiac surgery. However, few studies have investigated the association between HD and acute DeBakey type I aortic dissection (ADIAD) surgery. This retrospective study aimed to identify risk factors for developing HD in patients who received acute type I aortic dissection repair and its consequences. Methods A total of 830 consecutive patients who received ADIAD surgery from January 2014 to December 2019 at our center were screened for this study. The End-Stage Liver Disease (MELD) score more than 14 was applied to identify postoperative HD. Logistic regression model was applied to identify risk factors for postoperative HD, Kaplan–Meier survival analysis and Cox proportional hazards regression assay were conducted to analyze the association between HD and postoperative long-term survival. Results Among 634 patients who eventually enrolled in this study, 401 (63.2%) experienced postoperative HD with a 30-Day mortality of 15.5%. Preoperative plasma fibrinogen level (PFL) [odds ratio (OR): 0.581, 95% confidence interval (CI): 0.362–0.933, P = 0.025], serum creatinine (sCr) on admission (OR: 1.050, 95% CI 1.022–1.079, P

Introduction: Dengue fever is one of the most common vector-borne infections worldwide and is now endemic in Kerala. Knowledge about changing clinical presentation of dengue fever is important for timely diagnosis and appropriate management. Aim: To document changing trends in clinical presentation and course of illness among patients admitted with dengue fever in Kerala, India. Materials and Methods: This hospital-based, retrospective, observational study was conducted at Government Medical College and Hospital, Kannur, Kerala, India, from September 2021 to June 2022. The patients with dengue fever, presented in seasonal epidemic of the year 2019 was compared to similar patients presented during the year 2014. Data regarding clinical presentation, duration of hospital stay, complications and haematological parameters of the study population was collected using prevalidated questionnaire. Descriptive data were expressed in frequency, percentage, mean and standard deviation. Continuous and discrete variables were compared by Welch’s t-test, whereas categorical variables were compared using Pearson’s Chi-square test. Results: Out of the total 184 patients studied, 91 were from 2014 and 93 from 2019. The major presenting complaints were fever, body aches, headache, nausea and vomiting, arthralgia, and retroorbital pain incidence of which were similar in both the study years. Patients admitted in 2019 have shorter duration of fever (5.78 vs 6.79 days), earlier onset of severe thrombocytopaenia (6.62 vs 7.27 days) and delayed onset of complications (5.56 vs 3.6 days) compared to those admitted in 2014. They also had higher incidence of thrombocytopaenia (70.97% vs 54.94%) and complications (49.46% vs 14.29%) during the course of their illness. Conclusion: The study indicates towards a significant shift in clinical presentation of dengue fever in Kerala which may influence the admission and monitoring protocol of dengue fever patients in the years to come.

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction.DiscussionViral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver.ConclusionDuring the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.

A 10-year-old, female spayed Labrador Retriever was referred for acute hepatopathy and urinary retention. Blood work from the initial presentation (day 0) revealed a severe, mixed hepatopathy. Over the course of the patient’s hospitalization, the patient developed liver insufficiency. Urine was submitted for toxicological screening and revealed detection of a trace concentration of alpha-amanitin. The patient was treated supportively for alpha-amanitin intoxication and was discharged from the hospital on day 8, with most biochemical parameters being markedly improved. The patient was persistently hyporexic at the time of discharge. On day 15, at a recheck appointment, the patient had lost 2.4 kg and liver enzymology revealed improved values. On day 24, the patient was presented for anorexia and vomiting and had lost another 2.3 kg. Blood work and endocrinological testing at that time were consistent with hypoadrenocorticism. The patient was started on glucocorticoids and mineralocorticoids. At day 106, the patient was doing well clinically while receiving monthly mineralocorticoids and daily glucocorticoids. This case report is the first to describe the chronological association between alpha-amanitin-induced liver dysfunction and the subsequent development of adrenal insufficiency in a dog.

Introduction: Dose adjustments in patients with renal or hepatic dysfunction using anticancer drugs are indicated according to guidelines. However, implementation depends on awareness of prescribing physicians. We implemented a Clinical Decision Support System (CDSS), recommending dose adjustments upon electronic prescriptions based on renal and hepatic function. The alert provides a dose adjustment proposal and recent laboratory results. Our objective was to determine the frequency of dose adjustments before and after implementation of this CDSS. Methods: We included all first orders for patients ≥18 years treated with parenteral antineoplastic agents, for whom dosage adjustment is necessary based on renal or hepatic function between February 2018 and January 2019. This study was performed at the department of Clinical Oncology and Hematology of the Amsterdam University Medical Center. We implemented the CDSS August first. All prescriptions were prescribed according to common practice. We analyzed the orders where a dose reduction based on renal or hepatic function was indicated. Results: We included 73 orders before implementation and 99 orders after implementation. Before implementation 21% of doses were reduced in line with the guidelines versus 34% after implementation (p = 0.048). For hepatic dysfunction the proportion changed from 11% to 46% p = 0.011, while there was no effect for renal dysfunction (24% vs. 26% p = 0.75). Conclusion: Dosages are more frequently adjusted in concordance with guidelines in patients with hepatic dysfunction who are treated with parenteral antineoplastic agents after implementation of a CDSS. The change was not seen in patients with renal dysfunction. [ABSTRACT FROM AUTHOR]

Weil's syndrome, a severe form of the disease, may present with symptoms such as jaundice, renal dysfunction, and hemorrhagic diathesis and it can progress to multi-organ failure leading to death. In patients with coinfection of tuberculosis with leptospirosis, there may be severe hepatic and renal dysfunction rendering the standard antitubercular therapy (ATT) regimen useless, thus requiring alternate drug selection and dose modification of antitubercular drugs. We present a case of a 57-year-old female who presented with high-grade fever and yellowish discoloration of the eyes. She was diagnosed with Weil's disease and started on treatment. She later developed altered sensorium and lumbar puncture was suggestive of tubercular meningitis. Due to her deranged renal and hepatic function tests, she was started on a modified regimen of ATT with intermittent dialysis. The patient responded to treatment and was shifted to the standard Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE) regimen once renal and hepatic functions returned to normal.