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International Journal Of Hepatology[JOURNAL]

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Clinical Profile and Limitations in the Management of HBV Patients Attending Clinic at a District Hospital in Ghana.

Duah A, Nartey YA

Int J Hepatol · 2023 · PMID 36643337 · Full text

BACKGROUND: Chronic hepatitis B (CHB) is estimated to cause between 500,000 and 1.2 million deaths worldwide every year through cirrhosis and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC are the commonest live... BACKGROUND: Chronic hepatitis B (CHB) is estimated to cause between 500,000 and 1.2 million deaths worldwide every year through cirrhosis and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC are the commonest liver diseases causing death in Ghana. The most critical problem in the management of CHB in sub-Saharan Africa is the high cost of investigations and antiviral drugs. There is scanty information concerning newly diagnosed CHB patients and their management challenges in Ghana. This study sought to determine the clinical characteristics and management challenges of CHB patients in Ghana. . A prospective cohort study was conducted involving newly diagnosed CHB patients being managed at St. Dominic Hospital. Patient demographic and clinical features were abstracted using a standardized questionnaire. The proportion of patients able to undertake investigations and treatment were determined, and the limitations to standard management were recorded. The performance of APRI score in the diagnosis of cirrhosis was also investigated. RESULTS: Of the 334 patients with newly diagnosed CHB, the median age at diagnosis was 35 (IQR 28-44) years. Less than a quarter (22.2%) were able to undertake viral load testing and 23.4% were eligible for treatment. Of those who were eligible for treatment, only 42.3% were able to initiate treatment. Almost a third of cases (32.1%) reported late with liver-related complications. The sensitivity of APRI score with cut-off value of 2 in the diagnosis of liver cirrhosis was 70.2% and specificity was 97.9%. CONCLUSION: A high proportion of newly diagnosed CHB patients presented late and with liver-related complications. Majority were not able to afford viral load testing and antiviral medication. Screening of hepatitis B among the general population and inclusion of CHB management in the National Health Insurance Scheme should be encouraged.

Hepatitis C Seroconversion Remains High among Patients with Regular Hemodialysis: Study of Associated Risk Factors.

Dharmesti NWW, Wibawa IDN, Kandarini Y

Int J Hepatol · 2022 · PMID 36618760 · Full text

METHODS: An analytical cross-sectional study involving patients from 2 dialysis units (1 referral hospital and 1 private dialysis unit) in Denpasar, Bali, Indonesia, from January 2020 to December 2021. We evaluated age,... METHODS: An analytical cross-sectional study involving patients from 2 dialysis units (1 referral hospital and 1 private dialysis unit) in Denpasar, Bali, Indonesia, from January 2020 to December 2021. We evaluated age, gender, duration of hemodialysis, vascular access, history of transfusion, history of surgery, diabetes mellitus, hepatitis B, human immunodeficiency virus (HIV) infection, and type of dialyzer as possible risk factors of hepatitis C seroconversion among hemodialysis patients. RESULTS: A total of 338 hemodialysis patients were enrolled in this study. We found hepatitis C seroconversion in 94 patients (27.8%), all of which occurred after regular dialysis was started. Vascular access type (OR 42.07, 95% CI 5.757-307.472) and dialyzer reuse (OR 8.324, 95% CI 4.319-16.044) were showing a statistically significant association with hepatitis C seroconversion. A separate analysis on each dialysis unit found common evidence that the duration of dialysis was significantly associated with hepatitis C infection among hemodialysis patients. CONCLUSION: Hepatitis C seroconversion among dialysis patients remains high. Factors related to the dialysis procedure itself played a major role in transmitting the virus.

Assessment of Clinical Characteristics and Outcomes of Liver Diseases Unique to Pregnancy at a Tertiary Hospital in Ethiopia: A Retrospective Cohort Study.

Mekonnen S, Fisseha H, Getinet T

Int J Hepatol · 2022 · PMID 36578273 · Full text

BACKGROUND: Liver disease is a rare complication of pregnancy that can lead to several consequences and require specific intervention with implications for both the mother and fetus. This study is aimed at assessing the... BACKGROUND: Liver disease is a rare complication of pregnancy that can lead to several consequences and require specific intervention with implications for both the mother and fetus. This study is aimed at assessing the clinical profile and associated complications of liver diseases unique to pregnancy at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. . This study is a retrospective cohort study of all identified cases admitted to the obstetrics ward and intensive care unit (ICU) from January 2018 to December 2020 at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia. Medical records were reviewed for clinical features, biochemical profiles, and fetomaternal complications. Data were analyzed using SPSS version 26. A chi-square test was done to look for an association with a value less than 0.05 considered statistically significant, and an odds ratio was determined to assess the effect size. RESULTS: From 95 cases identified, preeclampsia/eclampsia with liver dysfunction accounted for 43 (45%), followed by hemolysis elevated liver enzyme and low platelet (HELLP syndrome) 35 (36.8%), hyperemesis gravidarum with liver dysfunction 9 (9.5%), acute fatty liver of pregnancy (AFLP) 7 (7.4%), and intrahepatic cholestasis of pregnancy 1 (1.1%). When compared to HELLP syndrome, AFLP showed significantly higher median (IQR) values ( < 0.05) for total bilirubin 13.3 (7.3-16.3), direct bilirubin 9.73 (6.87-11.9) mg/dL, prothrombin time 23 (20.4-25.7) seconds, international normalization ratio 2.2 (1.9-2.4), white blood count 23.8 (17.8-26.6)10/L, creatinine 3.5 (2.44-5.6) mg/dL, and lower hemoglobin level of 7.9 (6.2-10) g/dL. There were 4 (4.2%) maternal hospital deaths, with a case fatality rate of HELLP syndrome being 8.6% and 14.3% in AFLP. The overall hospital fetal mortality was 33 (34.7%). In this study, 42 patients with HELLP syndrome and AFLP had an increased risk of maternal ICU admission (OR = 25.5, 95% CI: 5.48-118.6, value = 0.001), acute kidney injury requiring dialysis (OR = 12.2, 95% CI: 1.46-102.2, value = 0.009), placental abruption (OR = 14.2, 95% CI: 1.72-117.1, value = 0.004), and stillbirth (OR = 7.2, 95% CI: 2.38-21.7, value = 0.001). CONCLUSION: Preeclampsia with liver dysfunction and HELLP syndrome accounted for the majority of cases. It also demonstrated key biochemical characteristics that can be used to distinguish between HELLP syndrome and AFLP. Emphasis has to be given to the risk of requiring maternal ICU admission, dialysis, abruption of the placenta, and stillbirths while managing patients diagnosed with HELLP syndrome and AFLP.

Serological Evidence of Hepatitis B and E and Dengue Coinfection in Chadian Patients and Impact on Lipidemia Profile.

Djasrabe AK, Tietcheu Galani BR, Ali MM … +4 more , Yandai FH, Nadlaou B, Habkreo M, Njintang NY

Int J Hepatol · 2022 · PMID 36158230 · Full text

OBJECTIVE: Viral hepatitis is an endemic disease in Chad. However, few studies have documented coinfection cases and their impact on cardiovascular risk. This study is aimed at analyzing hepatitis B, E and dengue coinfec... OBJECTIVE: Viral hepatitis is an endemic disease in Chad. However, few studies have documented coinfection cases and their impact on cardiovascular risk. This study is aimed at analyzing hepatitis B, E and dengue coinfection in a Chadian cohort and gauge its effect on lipidemia. . From February to May 2021, 179 subjects were recruited from the Department of Gastroenterology and Internal Medicine of the National Reference University Hospital of N'Djamena and tested for viral hepatitis markers, including HBsAg and IgM/IgG anti-HEV and dengue infection, using the NS1/IgM/IgG kit. Serum transaminases and biomarkers of lipid profiles were assayed by colorimetry, and atherogenic indexes (AI) and coronary risk (CRI) were calculated. RESULTS: Of the 179 subjects surveyed, 21.22% (38/179) tested positive for hepatitis B, 20% (27/135) for hepatitis E, and 1.66% (2/120) for dengue. However, most of the patients were found to be asymptomatic. Hepatitis B/E coinfection was more frequent in the study population (5.02%; 9/179) than dengue/hepatitis E coinfection (0.83%; 1/120; IgM). The prevalence of anti-HEV IgG antibodies was higher (18.52%) than that of IgM (1.48%). Furthermore, IgG antibodies levels in HEV-monoinfected subjects (11.05 ± 1.93 IU/mL, = 15) were significantly higher ( < 0.05) than in coinfected patients (5.40 ± 1.31 IU/mL, = 9). Subjects coinfected with HEV/HBV were associated with a significantly higher risk of lipodystrophy (coronary risk: 88.89% vs. 35.3%, relative risk (RR) = 2.55; = 0.014), than HEV-monoinfected subjects, as evidenced by higher mean levels of triglycerides levels (219.88 ± 14.67 mg/dL vs. 191.82 ± 4.66  mg/dL, < 0.05), more reduced HDL-C levels (9.05 ± 1.62 mg/dL vs. 18.93 ± 2.35 mg/dL, < 0.05), increased mean CRI (13.81 ± 2.39 vs. 6.89 ± 1.93, < 0.01), and AI (1.46 ± 0.10 vs. 1.05 ± 0.05, < 0.01) values. However, they had normal transaminase values and a lower risk of developing a liver injury, although not significant (alanine aminotransferase: 0% vs. 29.4%, RR = 1, = 0.128; aspartate aminotransferase: 0% vs. 5.88%, = 1) than this group. CONCLUSION: HBV/HEV coinfection is frequent in the Chadian cohort and associated with an important risk of dyslipidemia. Further research is required to elucidate the mechanism of action.

Spleen and Liver Stiffness Evaluation by ARFI Imaging: A Reliable Tool for a Short-Term Monitoring of Portal Hypertension?

Binzberger A, Hänle M, Pfahler M … +3 more , Kratzer W, Seufferlein T, Zizer E

Int J Hepatol · 2022 · PMID 36117519 · Full text

BACKGROUND: Assessment of hepatic venous pressure gradient (HVPG) is the most reliable, though invasive method for evaluation of portal hypertension. Non-invasive, elastography-based techniques are well established in di... BACKGROUND: Assessment of hepatic venous pressure gradient (HVPG) is the most reliable, though invasive method for evaluation of portal hypertension. Non-invasive, elastography-based techniques are well established in diagnosis, but not in monitoring of portal hypertension. The aim of our prospective study was to determine the value of acoustic radiation force impulse (ARFI) elastography technique of the liver and spleen in diagnosis and monitoring of portal hypertension. METHODS: We prospectively assessed portal hypertension by HVPG and corresponding elastography of the liver and spleen in 31 patients with liver cirrhosis and an indication for primary prophylaxis by non-cardio selective beta-blockers. Investigations were performed at baseline and a follow-up visit after 6-8 weeks. To address the known large variability of values for spleen elastography, well-defined corresponding areas in the spleen were used for baseline and follow-up elastography. Sensitivity, specificity, and AUC-ROC values for both spleen and liver elastography monitoring of portal hypertension were calculated. RESULTS: Liver but not spleen elastography significantly correlated with HVPG results and was suitable for initial evaluation of portal hypertension. However, changes in HVPG results did not show any correlation with alterations of ARFI values from baseline to follow-up visits both for liver and spleen elastography. Spleen stiffness results were not homogeneous across the whole organ differing significantly between the upper, hilar, and bottom placed investigation areas. CONCLUSIONS: In this prospective study ARFI-based assessment of liver elastography showed itself suitable for initial assessment but not for monitoring of portal hypertension. Spleen elastography was not appropriate for both, evaluation and monitoring of portal hypertension. A possible explanation for this new data that are in some contrast to previously published results is the degree of portal hypertension in our study, a comparatively short follow-up period, and well-defined investigation areas for spleen elastography in repetitive ARFI investigations. This trial is registered with NCT03315767.

Arsenic-Induced Injury of Mouse Hepatocytes through Lysosome and Mitochondria: An In Vitro Study.

Santra A, Bishnu D, Santra S … +4 more , Ghatak S, Mukherjee PS, Dhali GK, Chowdhury A

Int J Hepatol · 2022 · PMID 36117518 · Full text

BACKGROUND AND AIMS: The cellular mechanism of liver injury related to arsenic toxicity is ill defined. It is thought that oxidative stress and mitochondrial dysfunction may play some role in arsenic-induced liver damage... BACKGROUND AND AIMS: The cellular mechanism of liver injury related to arsenic toxicity is ill defined. It is thought that oxidative stress and mitochondrial dysfunction may play some role in arsenic-induced liver damage. In this study, we evaluated subcellular events within the primary cultured mouse hepatocytes when exposed to inorganic arsenic. METHODS: Primary cultured mouse hepatocytes were treated with 10 M arsenic for different time periods. Reactive oxygen species (ROS) formation, functional changes of the lysosome and mitochondria, and mode of hepatocytes death were studied by laser confocal microscopy, fluorescence spectroscopy, and flow cytometry. Expression of proapoptotic member of the BCL-2 family of genes BAX and antiapoptotic BCL-2 mRNA expression were studied by real-time PCR. Cytochrome c expression was studied by Western blotting. RESULTS: Fluorescence spectroscopy as well as flow cytometric analysis revealed that arsenic-induced formation of ROS was time dependent. Confocal microscopy showed initiation of ROS formation from periphery of the hepatocytes at 30 min of arsenic exposure that progressed to central part of the hepatocytes at 3 h of arsenic exposure. The ROS formation was found to be NADPH oxidase (NOX) dependent. This low level of intracellular ROS induced lysosomal membrane permeabilization (LMP) and subsequently released cathepsin B to the cytosol. The LMP further increased intracellular ROS which in turn triggered induction of mitochondrial permeability transition (MPT). Pretreatment of hepatocytes with LMP inhibitor bafilomycin A (BafA) significantly decreased, and LMP inducer chloroquine (ChQ) significantly increased the production of ROS suggesting that LMP preceded enhanced ROS generation in response to arsenic. MPT was accompanied with increase in BAX : BCL2 mRNA ratio resulting in upregulation of caspase 3 and increased hepatocyte apoptosis. CONCLUSION: Although arsenic-related oxidative liver injury is well established, neither the site of origin of ROS nor the early sequence of events in arsenic toxicity due to ROS is known. We believe that our study provides evidences elucidating the early sequence of events that culminates in the death of the mouse hepatocytes during arsenic exposure.

Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants.

Turyadi, Witanto B, El-Khobar KE … +9 more , Parewangi ML, Rasyak MR, Wibowo DP, Thedja MD, Yusuf I, Massi MN, Patellongi I, Syafruddin D, Muljono DH

Int J Hepatol · 2022 · PMID 36052277 · Full text

BACKGROUND: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF- and IL-10, have been associated with... BACKGROUND: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF- and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF- (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. METHODS: A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF- and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. RESULTS: No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF- rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, = 0.004). CONCLUSIONS: Age and male gender were associated with CHB phase progression instead of the TNF- and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

Practice towards Hepatitis B Virus Infection Prevention and Its Associated Factors among Undergraduate Students at Hawassa University College of Medicine and Health Sciences, Hawassa, Sidama, Ethiopia, 2021: Cross-Sectional Study.

Aynalem A, Deribe B, Ayalew M … +4 more , Mamuye A, Israel E, Mebratu A, Assefa DG

Int J Hepatol · 2022 · PMID 35991003 · Full text

BACKGROUND: Hepatitis B virus infection is a major global health burden accounting for 2.7% of all deaths globally. Being part of the health care system, the risk of exposure to hepatitis B viral infection among medical... BACKGROUND: Hepatitis B virus infection is a major global health burden accounting for 2.7% of all deaths globally. Being part of the health care system, the risk of exposure to hepatitis B viral infection among medical and health science students is found to be high. In Ethiopia, particularly in this study area, very little is known about the practice of students towards hepatitis B virus infection prevention and its associated factors. OBJECTIVE: The aim of this study was to assess the practice towards hepatitis B virus infection prevention and its associated factors among undergraduate students at Hawassa University College of Medicine and Health Sciences, Hawassa, Ethiopia, 2021. METHODS AND MATERIALS: An institution-based cross-sectional study was conducted from May 15 to June 15, 2021, among undergraduate students who had clinical exposure. The 404 sampled participants were recruited using a systematic random sampling technique. Data was collected using a structured self-administered questionnaire. Data was entered into EpiData version 4.6.0 and was exported to SPSS version 25 for analysis. Association between the dependent and independent variables was computed using the bivariate and multivariate logistic regression model. Odds ratio was calculated. Results were interpreted as significant if value is <0.05 at 95% CI. RESULT: This study revealed that 277 (69.9%) of the students were in the age group of 20-24 years and 266 (67.2%) were males. Out of 396 participants, about half 199 (50.3%) 95% CI (0.452-553) had a good practice towards hepatitis B virus infection prevention. Only 43.4% of the study participants had been completely vaccinated against hepatitis B virus. Age (20-24 years) (AOR = 2.736), 95% CI (1.130-6.625), and good knowledge (AOR = 1.990), 95% CI (1.207-3.282) were factors significantly associated with the practice towards hepatitis B virus infection prevention. . The current study showed that about half of the study participants had good practice towards hepatitis B virus infection prevention but more than half were not completely vaccinated against HBV. Age and knowledge were factors significantly associated. It is recommended to give training for students on hepatitis B virus infection prevention. It is also advisable to screen and vaccinate students before they start their clinical attachments.

Pregnancy Is Not Associated with an Increased Risk of Decompensation, Transplant, or Death in Compensated Cirrhosis.

Mullin M, Djerboua M, Sarkar M … +5 more , Lu J, Velez MP, Brogly S, Terrault NA, Flemming JA

Int J Hepatol · 2022 · PMID 35845752 · Full text

BACKGROUND AND AIMS: Childbirth in women with cirrhosis is increasing and associated with a higher risk of perinatal outcomes compared to the general population. Whether pregnancy influences the risk of liver-related eve... BACKGROUND AND AIMS: Childbirth in women with cirrhosis is increasing and associated with a higher risk of perinatal outcomes compared to the general population. Whether pregnancy influences the risk of liver-related events compared to nonpregnant women with cirrhosis is unclear. This study evaluates the association between pregnancy and liver-related outcomes in women with compensated cirrhosis. . Population-based retrospective matched cohort study in Ontario, Canada, using routinely collected healthcare data. Pregnant women with compensated cirrhosis and without prior history of decompensation between 2000 and 2016 were identified and matched to nonpregnant women with compensated cirrhosis on age, etiology of cirrhosis, and socioeconomic status in a 1 : 2 ratio. The association between pregnancy and the composite outcome of nonmalignant decompensation, liver transplant (LT), and death up to two years after cohort entry was estimated using the multivariate Cox proportional hazard regression adjusting for potential confounders. Overall, 5,403 women with compensated cirrhosis were included (1,801 pregnant; 3,602 nonpregnant; median age 31 years (IQR 27-34); 60% nonalcoholic fatty liver disease, 34% viral hepatitis). After two years of follow-up, only 19 (1.1%) pregnant women had a liver-related event compared to 319 (8.9%) nonpregnant women. Pregnant women with compensated cirrhosis had a lower hazard of a liver-related event compared to nonpregnant women (aHR 0.14, 95% CI 0.09-0.22, < .001). CONCLUSIONS: Pregnancy in women with compensated cirrhosis is not associated with increased liver-related events compared to nonpregnant women. These results can facilitate counselling women with cirrhosis of child-bearing age and suggests that pregnancy may not accelerate liver disease progression.

Knowledge, Attitude, Practices, and Associated Factor towards Hepatitis B Virus Infection among Health Care Professionals at Tibebe Ghion Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2021: A Cross Sectional Study.

Belete D, Wondale D, Kiros T … +1 more , Demissie B

Int J Hepatol · 2022 · PMID 35572163 · Full text

BACKGROUND: Hepatitis B virus (HBV) infection is the major infectious hazard for health care personnel. The global prevalence of HBV infection is highly heterogeneous, and the highest prevalence (6.2 and 6.1%) is among t... BACKGROUND: Hepatitis B virus (HBV) infection is the major infectious hazard for health care personnel. The global prevalence of HBV infection is highly heterogeneous, and the highest prevalence (6.2 and 6.1%) is among the World Health Organization Western Pacific and World Health Organization African regions, respectively. The pooled prevalence of HBV in Ethiopia among health workers was accounted for 5%. The prevalence rate of HBV in health care workers is about 2-10 times higher than the general population in the world. There for, the main aim of this study was to assess the knowledge, attitude and practice, and associated factors towards hepatitis B virus (HBV) infection among health care professionals at Tibebe Ghion Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2021. METHOD: An institutional-based cross-sectional study design was at Tibebe Ghion Specialized Hospital, Bahir Dar, in 2021, and a systematic random sampling technique was used from different professionals, and the separate sample was taken independently from each. A pretested structured questionnaire was constructed and collects data then analyzed by using SPSS version 23. RESULT: A total of 422 health care workers having different professions have participated in this study. 243 (57.6%) of the study subjects were males. The average correctly answered knowledge, attitude, and practice questions were 65.6%, 40.3%, and 34.8, respectively. Multivariable logistic regression analysis showed that being nurse professionals ( = 0.17 (0.07, 0.38), < 0.001), midwives ( = 0.19 (0.07, 0.5), = 0.001), and work experience ( = 2.37 (1.38, 4.02), = 0.002) were associated with knowledge levels. Being degree holders ( = 2.49 (1.23, 5.02), = 0.01) and specialists ( = 9.78 (2.69, 35.5), = 0.001) were associated with attitude levels. Being medical laboratories ( = 17.42 (5.02, 60.5), ≤ 0.001) and pharmacy professionals ( = 11.2 (4.02, 31.42), ≤ 0.001) were associated with practice levels. . Based on the current study, most of the health care professionals in this study area have poor knowledge, negative attitude, and malpractice towards HBV infection. Therefore, continual professional training programs on HBV infection include increased vaccination coverage rate and postexposure prophylaxis of heath care workers especially for highly exposed professionals.

Clinical Characteristics of Patients with Hepatocellular Carcinoma: A Single-Center 3-Year Experience from Somalia.

Hassan-Kadle MA, Osman MM, Keles E … +4 more , Eker HH, Baydili KN, Ahmed HM, Osman AA

Int J Hepatol · 2022 · PMID 35411218 · Full text

BACKGROUND: To evaluate the relationship between prognosticators representing tumor aggressiveness and socio-demographic, laboratory, and imaging findings in patients with hepatocellular carcinoma (HCC). METHODS: We retr... BACKGROUND: To evaluate the relationship between prognosticators representing tumor aggressiveness and socio-demographic, laboratory, and imaging findings in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively searched patients with HCC between January 2017 and December 2019 in our tertiary referral hospital. The tumor-related factors and liver damage indicators and their relationship to indicate the value of prognosis were analyzed. RESULTS: A total of 268 HCC patients, with a male-to-female ratio of 2.8 : 1. The mean age was 52.6 years. The patient with portal vein thrombosis (PVT) was older, had higher liver laboratory parameters (AST, ALT, total bilirubin, and direct bilirubin), and had larger tumor size. Patients with the larger tumor size had a higher AFP level, had more tumor multifocality. The majority of patients were in Child's A (73.6%) and B (17.2%) classes. The laboratory parameters of HCC patients were increased in Child's C compared to other groups of Child-Pugh classification. CONCLUSIONS: The presence of PVT and large-sized tumor in patients with HCC indicated a poorer prognosis than non-PVT group and small tumor sizes.

Urinary BA Indices as Prognostic Biomarkers for Complications Associated with Liver Diseases.

Li W, Alamoudi JA, Gautam N … +5 more , Kumar D, Olivera M, Gwon Y, Mukgerjee S, Alnouti Y

Int J Hepatol · 2022 · PMID 35402050 · Full text

Hepatobiliary diseases and their complications cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may exacerbate the underlying condition and lead to unfavorable prognosis. To d... Hepatobiliary diseases and their complications cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may exacerbate the underlying condition and lead to unfavorable prognosis. To develop and validate prognostic biomarkers for the prediction of complications of cholestatic liver disease based on urinary BA indices, liquid chromatography-tandem mass spectrometry was used to analyze urine samples from 257 patients with cholestatic liver diseases during a 7-year follow-up period. The urinary BA profile and non-BA parameters were monitored, and logistic regression models were used to predict the prognosis of hepatobiliary disease-related complications. Urinary BA indices were applied to quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. We have developed and validated the bile-acid liver disease complication (BALDC) model based on BA indices using logistic regression model, to predict the prognosis of cholestatic liver disease complications including ascites. The mixed BA and non-BA model was the most accurate and provided higher area under the receiver operating characteristic (ROC) and smaller akaike information criterion (AIC) values compared to both non-BA and MELD (models for end stage liver disease) models. Therefore, the mixed BA and non-BA model could be used to predict the development of ascites in patients diagnosed with liver disease at early stages of intervention. This will help physicians to make a better decision when treating hepatobiliary disease-related ascites.

Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management.

Kafeero HM, Ndagire D, Ocama P … +11 more , Kato CD, Wampande E, Kajumbula H, Kateete D, Walusansa A, Kudamba A, Edgar K, Katabazi FA, Namaganda MM, Ssenku JE, Sendagire H

Int J Hepatol · 2022 · PMID 35070455 · Full text

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a... BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. METHODS: A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson's chi-square, multinomial logistic regression, and Mann-Whitney tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A < 0.05 was considered statistically significant. RESULTS: Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly ( < 0.05). Genotype D was significantly associated with elevated viral load and direct bilirubin ( < 0.05). The recombinant genotype D/E was significantly associated with elevated viral load ( < 0.05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels ( < 0.05). CONCLUSION: There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.

Role of High-Density Lipoprotein Cholesterol (HDL-C) as a Clinical Predictor of Decompensation in Patients with Chronic Liver Disease (CLD).

Rao B H, Nair P, Koshy AK … +3 more , Krishnapriya S, Greeshma CR, Venu RP

Int J Hepatol · 2021 · PMID 34976412 · Full text

INTRODUCTION: Systemic inflammation triggered by bacterial products like lipopolysaccharides (LPS) in the circulation is an important factor leading to decompensation in patients with chronic liver disease (CLD). High-de... INTRODUCTION: Systemic inflammation triggered by bacterial products like lipopolysaccharides (LPS) in the circulation is an important factor leading to decompensation in patients with chronic liver disease (CLD). High-density lipoprotein cholesterol (HDL-C) has a significant role in innate immune response to LPS in the circulation and could therefore increase the risk for decompensation in patients with CLD. In this study, we have explored the role of HDL-C as a prognostic marker for decompensation. METHODS: This was a prospective, observational, cohort study where consecutive patients with CLD were included. Patients with cholestatic liver disease and hepatocellular carcinoma were excluded. Fasting lipids were measured in all patients at the time of recruitment. Each patient was carefully followed up for development of decompensation events such as new-onset/worsening ascites, hepatic encephalopathy, or variceal bleed during follow-up. RESULTS: A total of 170 patients were included (mean age 60 ± 11.5 years, M : F = 6 : 1). At the end of follow-up, 97/170 patients (57%) had decompensation events. Mean HDL-C levels were significantly lower among patients with decompensation (27.5 ± 15 mg/dL vs. 43.5 ± 13.9 mg/dL; value 0.004). Using ROC analysis, cut-off for HDL-C of 36.4 mg/dL was identified. On multivariate analysis, HDL-C (OR = 6.072; 95% CI 2.39-15.39) was found to have an independent association with risk of decompensation. CONCLUSIONS: HDL-C level (<36.4 mg/dL) is a reliable marker for risk of decompensation and can be a useful addition to existing prognostic scoring systems in CLD. It can be a valuable tool to streamline treatment protocols and prioritise liver transplantation.

Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis.

Behera MK, Swain SN, Sahu MK … +6 more , Behera GK, Mishra D, Narayan J, Singh A, Agarwal S, Mallick PK

Int J Hepatol · 2021 · PMID 34900353 · Full text

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcom... BACKGROUND: Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcome of liver transplantation or TIPS insertion, a few Indian studies have addressed the role of LVDD on survival in decompensated cirrhosis. The objective of this study is to assess the effect of LVDD on the survival of decompensated cirrhotic patients. METHODS: We prospectively evaluated 92 decompensated cirrhotic patients from April 2015 to March 2017 at IMS and SUM Hospital, Bhubaneswar, India. 2D echocardiography with tissue Doppler imaging was used to evaluate cardiac function, as per the American society of echocardiography guidelines. The primary endpoint was to evaluate the effect of LVDD on overall mortality. RESULTS: Ninety-two decompensated cirrhotic patients were evaluated in this prospective cohort study. Twenty-eight out of 92 patients (30%) died due to liver-related complications after a follow-up of 24 months. The decompensated cirrhotic patients with MELD score ≥ 15 had a significantly higher /' ratio (11.94 ± 4.24 vs. 8.74 ± 3.32, < 0.001) suggesting severe LV dysfunction in advanced cirrhosis. Patients with /' ratio > 10 had significantly higher MELD score and Child-Pugh score (19.88 ± 7.72 vs. 14.31 ± 5.83; 10.25 ± 1.74 vs. 9.02 ± 1.74, < 0.01, respectively) as compared to the/' ratio < 10 group. In Cox proportional hazard multivariate analysis, /' ≥ 10 (HR 2.72, 95% CI 1.07-6.9, = 0.03) and serum albumin (HR 0.32, 95% CI 0.14-0.7, < 0.01) were found to be independent predictors of mortality in decompensated cirrhotic patients. CONCLUSION: : The presence of LVDD and low serum albumin were independent predictors of mortality in decompensated cirrhotic patients. Hence, LVDD is an indicator of advanced cirrhosis and mortality.

Supplementation with Branched-Chain Amino Acids Induces Unexpected Deleterious Effects on Astrocyte Survival and Intracellular Metabolism with or without Hyperammonemia: A Preliminary In Vitro Study.

Wang T, Suzuki K, Chiba T … +2 more , Kakisaka K, Takikawa Y

Int J Hepatol · 2021 · PMID 34712496 · Full text

INTRODUCTION: Ammonia is a key component in the pathogenesis of hepatic encephalopathy. Branched-chain amino acids (BCAA) have been reported to improve the symptoms of HE induced by hyperammonemia; however, we recently r... INTRODUCTION: Ammonia is a key component in the pathogenesis of hepatic encephalopathy. Branched-chain amino acids (BCAA) have been reported to improve the symptoms of HE induced by hyperammonemia; however, we recently reported that ammonia increases intracellular levels of BCAA and exerts toxic effects on astrocytes. OBJECTIVES: This follow-up study was designed to confirm the direct effects of BCAA on human astrocytes and clarify their underlying mechanisms using metabolome analysis and evaluation of associated signaling. METHODS: We performed cytotoxicity and cell proliferation tests on astrocytes following BCAA treatment with and without ammonium chloride (NHCl) and then compared the results with the effects of BCAA on hepatocytes and neurons. Subsequently, we used metabolomic analysis to investigate intracellular metabolite levels in astrocytes with and without BCAA treatment. RESULTS: The astrocytes showed increased leakage of intracellular lactate dehydrogenase and reduced proliferation rate upon BCAA treatment. Interestingly, our analysis showed a BCAA-induced impairment of intracellular glycolysis/glyconeogenesis as well as amino acid and butyric acid metabolism. Furthermore, BCAA treatment was found to cause decreased levels of Glut-1 and phosphorylated GSK-3 and mTOR in astrocytes. CONCLUSIONS: Although further investigations of the effect of BCAA on human astrocytes with hyperammonemia are needed, our work demonstrates that BCAA supplementation has direct negative effects on astrocyte survival and intracellular metabolism.

Infrahepatic Inferior Vena Cava Clamping Reduces Blood Loss during Liver Transection for Cholangiocarcinoma.

Leeratanakachorn N, Luvira V, Tipwaratorn T … +9 more , Theeragul S, Jarearnrat A, Titapun A, Srisuk T, Kamsa-Ard S, Pugkhem A, Khuntikeo N, Pairojkul C, Bhudhisawasdi V

Int J Hepatol · 2021 · PMID 34484836 · Full text

BACKGROUND: Major hepatectomy is the mainstay of the treatment for cholangiocarcinoma. Infrahepatic inferior vena cava (IVC) clamping is an effective maneuver for reducing blood loss during liver transection. The impact... BACKGROUND: Major hepatectomy is the mainstay of the treatment for cholangiocarcinoma. Infrahepatic inferior vena cava (IVC) clamping is an effective maneuver for reducing blood loss during liver transection. The impact of this procedure on major hepatectomy for cholangiocarcinoma is unknown. This study evaluated the effect of infrahepatic IVC clamping on blood loss during liver transection. METHODS: Clinical and pathological data were collected retrospectively for 116 cholangiocarcinoma patients who underwent major hepatectomy between January 2015 and December 2016, to investigate the benefit of infrahepatic IVC clamping. Two of five surgeons adapted the policy performing infrahepatic IVC clamping during liver transection in all cases. Patients, therefore, were divided into those ( = 39; 33.6%) who received infrahepatic IVC clamping during liver transection (C1) and those ( = 77; 66.4%) who did not (C0). RESULTS: The patients' backgrounds, operative parameters, and extent of hepatectomy did not differ significantly between the 2 groups, except for gender. A significantly lower blood loss ( = 0.028), blood transfusion ( = 0.011), and rate of vascular inflow occlusion requirement ( < 0.001) were observed in the C1 group. The respective blood losses in the C1 group and the C0 group were 498.9 (95% CI: 375.8-622.1) and 685.6 (95% CI: 571-800.2) millilitres. CONCLUSIONS: The current study found infrahepatic IVC clamping during liver transection for cholangiocarcinoma reduces blood loss, blood transfusion, and rate of vascular inflow occlusion requirement.

Prevalence of Hepatic Encephalopathy from a Commercial Medical Claims Database in the United States.

Potnis A, VanMeter S, Stange J

Int J Hepatol · 2021 · PMID 34211786 · Full text

INTRODUCTION: Hepatic encephalopathy (HE), a complication of cirrhosis, is associated with increased healthcare resource utilization and mortality, and impaired quality of life. Information on the prevalence of HE in the... INTRODUCTION: Hepatic encephalopathy (HE), a complication of cirrhosis, is associated with increased healthcare resource utilization and mortality, and impaired quality of life. Information on the prevalence of HE in the US general population is limited. METHODS: Prevalence of HE was estimated by sequential stepwise data analysis of the Symphony Health anonymized patient-level data (APLD) claims database. First, patients ≥ 18 years with International Classification of Diseases ninth/tenth edition, clinical modification (ICD-9/10-CM), and codes for cirrhosis from 2018 medical and hospital claims were used to estimate prevalence of cirrhosis within the data set and number of patients with cirrhosis in the US general population. Second, patients diagnosed with cirrhosis in the APLD data set from 2015-2016 with an HE ICD-9/10-CM code within 1 year of cirrhosis diagnosis were used to deduce the prevalence of HE within the data set and estimate the number of patients with HE in the US general population. Last, US DiagnosticSource data on serum ammonia level laboratory results measured within ±2 days of a confirmed HE event were merged with the APLD HE data set, then applied to the US general population. RESULTS: Medical and hospital claims data were available for 272,256 patients with cirrhosis in 2018. An estimated 536,856 US adults had a diagnosis of cirrhosis (prevalence of 0.21%) in 2018. This proportion applied to the estimated number of patients with cirrhosis in the United States resulted in a prevalence estimate of 201,858 cirrhosis patients with HE in 2018. When factoring in serum ammonia data, prevalence was conservatively estimated as approximately 196,000 cirrhosis patients with HE and serum ammonia levels > 21 mol/L. CONCLUSIONS: In this longitudinal cohort-based study, it was estimated that ≈202,000 patients had HE in the United States in 2018, representing a considerable burden to society and payers.

The Influence of Donor and Recipient Complement C3 Polymorphisms on Liver Transplant Outcome.

Pires M, Underhill J, Douiri A … +7 more , Quaglia A, Jassem W, Bernal W, Heaton N, Morgan P, Thompson R, Tredger JM

Int J Hepatol · 2021 · PMID 34123432 · Full text

Despite early reports of an impact of complement C3 polymorphism on liver transplant patient and graft survival, subsequent evidence has been conflicting. Our aim was to clarify the contributions of donor and recipient C... Despite early reports of an impact of complement C3 polymorphism on liver transplant patient and graft survival, subsequent evidence has been conflicting. Our aim was to clarify the contributions of donor and recipient C3 genotype, separately and together, on patient and graft outcomes and acute rejection incidence in liver transplant recipients. Eight donor/recipient groups were analyzed according to their genotype and presence or absence of C3 F allele (FFFS, FFSS, FSFF, FSFS, FSSS, SSFF, SSFS, and SSSS) and correlated with clinical outcomes of patient survival, graft survival, and rejection. The further impact of brain death vs. circulatory death during liver donation was also considered. Over a median 5.3 y follow-up of 506 patients with clinical information and matching donor and recipient tissue, five-year patient and graft survival (95% confidence interval) were 90(81-91)% and 77(73-85)%, respectively, and 72(69-94)% were rejection-free. Early disadvantages to patient survival were associated with donor C3 F variant, especially in brain-death donors. Recipient C3 genotype was an independent determinant of graft survival by Cox proportional hazards analysis (hazard ratio 0.26, = 0.04), and the C3 F donor variant was again associated with worse liver graft survival, particularly in brain-death donors. C3 genotype did not independently determine rejection incidence, but a greater proportion of recipient C3 F carriers were rejection-free in the circulatory death, but not the brain-death cohort. Cox proportional hazards analysis revealed significant effects of acute rejection on patient survival (hazard ratio 0.24, = 0.018), of retransplantation on rejection risk (hazard ratio 6.3, = 0.009), and of donor type (circulatory-death vs. brain-death) on rejection incidence (hazard ratio 4.9, = 0.005). We conclude that both donor and recipient complement C3 genotype may influence patient and graft outcomes after liver transplantation but that the type of liver donor is additionally influential, possibly via the inflammatory environment of the transplant.

Patients with Hepatitis C Infection and Normal Liver Function: A Neuropsychological and Neurophysiological Assessment of Cognitive Functions.

Abrantes J, Torres DS, Brandão-Mello CE

Int J Hepatol · 2021 · PMID 34113467 · Full text

Several studies have proposed a link between chronic hepatitis C virus (HCV) infection and the development of cognitive disorders. However, the inclusion of confounding factors in their samples significantly limits the i... Several studies have proposed a link between chronic hepatitis C virus (HCV) infection and the development of cognitive disorders. However, the inclusion of confounding factors in their samples significantly limits the interpretation of the results. Therefore, here, we aimed to compare the neurophysiological and cognitive performance between patients with HCV infection and a control group after excluding other factors that may cause cognitive impairment. This cross-sectional, group-control, observational study was performed from September 12, 2014, to October 20, 2017. HCV-infected patients and healthy individuals between 18 and 77 years were considered eligible. The exclusion criteria included well-established causes of cognitive impairment, such as depression and cirrhosis. The participants were submitted to neuropsychological testing to evaluate global cognitive function (minimental), sustained attention, divided attention, selective attention, working memory, psychomotor speed, and executive function and to a neurophysiological evaluation using quantitative electroencephalograms and P300 cognitive evoked potentials. Among the 309 patients considered eligible for the study, we excluded 259 patients who had one or more characteristics from the preestablished exclusion criteria, 18 who did not undergo neuropsychological and neurophysiological testing, and five who exhibited depression. The final sample consisted of 27 patients each in the HCV and control groups. The groups did not differ in age, schooling, and sex. The patients in the HCV group exhibited poorer performances in the cognitive areas involving attention ( = 0.01), memory ( = 0.02), and psychomotor velocity ( = 0.04) apart from exhibiting prolonged latency in the P3b component ( = 0.03) and score ( = 0.02) of the P300 evoked cognitive potential. In this study performed with strict selection criteria, on conducting neuropsychological and neurophysiological evaluations, we detected the presence of cognitive impairment characterized by the involvement of attention, working memory, psychomotor processing speed, and memory in the HCV group.
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