Burden of Cirrhosis and Other Chronic Liver Diseases Caused by Specific Etiologies in China, 1990-2016:Findings from the Global Burden of Disease Study 2016

Objective To estimate the burden of cirrhosis and other chronic liver diseases caused by specific etiologies in China.Methods Data from the Global Burden of Disease Study 2016(GBD 2016)were used.We evaluated the burden by analyzing age-sex-province-specific prevalence,mortality,and disability-adjusted lifeyears(DALYs)of 33 provinces in China.Results From 1990 to 2016,prevalence cases in thousands increased by 73.7%from 6833.3(95%UI:6498.0–7180.6)to 11869.6(95%UI:11274.6–12504.7).Age-standardized mortality and DALY rates per100,000 decreased by 51.2%and 53.3%,respectively.Male and elderly people(aged≥60 years)preponderance were found for prevalence,mortality,and DALYs.The number of prevalence cases,deaths,and DALYs due to hepatitis C virus(HCV)increased by 86.6%,8.7%,and 0.9%,respectively.Also,age-standardized prevalence rates decreased in 31 provinces,but increased in Yunnan and Shandong.The Socio-demographic Index(SDI)values were negatively correlated with age-standardized mortality and DALY rates by provinces in 2016;the correlation coefficients were-0.817 and-0.828,respectively.Conclusion Cirrhosis and other chronic liver diseases remain a huge health burden in China,with the increase of population and the aging of population.Hepatitis B virus(HBV)remains the leading cause of the health burden in China.

Peripheral blood lymphocytes DNA in patients with chronic liver diseases

BACKGROUND: Viral replication in blood cells with nucleases may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions. AIM: Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL) DNA in the patients with chronic liver diseases. MATERIALS AND METHODS: Sixteen-nine patients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol+virus G), 30 women with primary biliary cirrhosis-PBC) were examined. The condition of DNA structure of PBL was measured by the fluorescence analysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (the presence of DNA single-stranded breaks and alkalinelabile sights). RESULTS AND CONCLUSION: The quantity of DNA single-stranded breaks and alkalinelabile sights in DNA in all patients with chronic viral hepatitis didn't differ from the control group, excluding the patients with chronic hepatitis (CH) C+G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity. This fact may be connected with hypothesis about the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednisone was demonstrated. Probably, the tendency to increase the quantity of DNA single stranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.

Compensated liver cirrhosis:Natural course and disease-modifying strategies

Compensated liver cirrhosis(CLC)is defined as cirrhosis with one or more decompensating events,such as ascites,variceal haemorrhage,or hepatic encephalopathy.Patients with CLC are largely asymptomatic with preserved hepatic function.The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors.The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis,as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years.Furthermore,early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition.With the advent of effective non-invasive tools for detecting hepatic fibrosis,more and more patients with CLC are currently being recognised.This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or,at the very least,prevent its progression.There are numerous emerging approaches for preventing or delaying decompensation in CLC patients.A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression,and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension.Additionally,address-ing various cofactors(such as obesity,diabetes,dyslipidaemia,and alcoholism)and precipitating factors(such as infection,viral hepatitis,and hepatotoxic drugs)that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC.However,high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these diseasemodifying techniques for CLC patients.This article discussed the natural history of CLC,risk factors for its progression,and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.

Kidneys in chronic liver diseases

Acute kidney injury(AKI),defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL,occurs in about 20% of patients hospitalized for decompensating liver cirrhosis.Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state,reduced effective blood volume and stimulation of vasoconstrictor hormones.The most common causes of AKI in cirrhosis are pre-renal azotemia,hepatorenal syndrome and acute tubular necrosis.Differential diagnosis is based on analysis of circumstances of AKI development,natriuresis,urine osmolality,response to withdrawal of diuretics and volume repletion,and rarely on renal biopsy.Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients.AKI is one of the last events in the natural history of chronic liver disease,therefore,such patients should have an expedited referral for liver transplantation.Hepatorenal syndrome(HRS) is initiated by progressive portal hypertension,and may be prematurely triggered by bacterial infections,nonbacterial systemic inflammatory reactions,excessive diuresis,gastrointestinal hemorrhage,diarrhea or nephrotoxic agents.Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy.The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion,which is effective in about 50% of patients.The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt,renal vasoprotection or systems of artificial liver support.

Structural changes of proteins in liver cirrhosis and consequential changes in their function

The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

The Therapeutic Ways for Chronic Liver Diseases Accompanied by Diseases of the Endocrine and Mammary Glands

It is discovered by the authors of this article thatchronic hepatitis and hepatocirrhosis (hereinafterchronic hepatopathy for short) are often accompaniedby some diseases of endocrine and mammary glands.The authors have studied the pathogenesis andtreatment of the complications as presented in thefollowing.

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.

Chronic renal dysfunction in cirrhosis:A new frontier in hepatology

Chronic kidney disease(CKD)in patients with liver cirrhosis has become a new frontier in hepatology.In recent years,a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis.The rising prevalence of risk factors,such as diabetes,hypertension and nonalcoholic fatty liver disease,appears to have contributed significantly to the high prevalence of CKD.Moreover,the diagnosis of CKD in cirrhosis is now based on a reduction in the estimated glomerular filtration rate of<60 mL/min over more than 3 mo.This definition has resulted in a better differentiation of CKD from acute kidney injury(AKI),leading to its greater recognition.It has also been noted that a significant proportion of AKI transforms into CKD in patients with decompensated cirrhosis.CKD in cirrhosis can be structural CKD due to kidney injury or functional CKD secondary to circulatory and neurohormonal imbalances.The available literature on combined cirrhosis-CKD is extremely limited,as most attempts to assess renal dysfunction in cirrhosis have so far concentrated on AKI.Due to problems related to glomerular filtration rate estimation in cirrhosis,the absence of reliable biomarkers of CKD and technical difficulties in performing renal biopsy in advanced cirrhosis,CKD in cirrhosis can present many challenges for clinicians.With combined hepatorenal dysfunctions,fluid mobilization becomes problematic,and there may be difficulties with drug tolerance,hemodialysis and decision-making regarding the need for liver vs simultaneous liver and kidney transplantation.This paper offers a thorough overview of the increasingly known CKD in patients with cirrhosis,with clinical consequences and difficulties occurring in the diagnosis and treatment of such patients.

Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014

AIM To assess the etiology of chronic liver diseases(CLD) from 1998 to 2014 at the outpatient clinic of Gastroenterology of the main hospital in Northwest of Italy among those dedicated to hepatology.METHODS A random sample of charts of patients referred to for increased liver enzymes between January 1998 and December 2006, and between January 2012 and December 2014 were reviewed. Etiology search included testing for hepatitis B virus(HBV), hepatitis C virus(HCV), autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hereditary hemocromatosis. A risky alcohol consumption was also considered. Nonalcoholic fatty liver disease(NAFLD) was diagnosed in patients with histological and/or ultrasound evidence of steatosis/steatohepatitis, and without other causes of CLD.RESULTS The number of patients included was 1163. Of them, 528(45%) had positivity for HCV and 85(7%) for HBV. Among the virus-free patients, 417(36%) had metabolic disorders whereas the remaining had history of alcohol abuse, less prevalent causes of CLD or concomitant conditions. In comparison to 1998-2000(41%), a reduction of HCV alone-related cases was detected during the periods 2001-2003(35%, OR = 0.75, 95%CI: 0.53-1.06), 2004-2006(33%, OR = 0.70, 95%CI: 0.50-0.97) and 2012-2014(31%, OR = 0.64, 95%CI: 0.46-0.91). On the contrary, in comparison to 1998-2000(31%), metabolic-alone disorders increased in the period 2004-2006(39%, OR = 1.37, 95%CI: 0.99-1.91) and 2012-2014(41%, OR = 1.53, 95%CI: 1.09-2.16). The other etiologies remained stable. The increase of incidence of metabolic-alone etiology during the period 2004-2006 and 2012-2014 tended to be higher in older patients(≥ 50 years) compared to younger(P = 0.058).CONCLUSION In the Northwest of Italy, during this study period, the prevalence of HCV infection decreased notably whereas that of NAFLD increased.

Dynamic changes in liver function after transjugular intrahepatic portosystemic shunt in patients with cirrhosis

Purpose:To evaluate the dynamic changes in liver function after transjugular intrahepatic portosystemic shunt(TIPS)creation in patients with cirrhosis and to explore its association with clinical outcomes.Methods:This retrospective study included patients who underwent TIPS between August 2016 and December2020.Liver function was primarily evaluated using the model for end-stage liver disease(MELD)score,which was analyzed at baseline,1 week,1 month,3 months,6 months,and 12 months using one-way repeated measures ANOVA.The Kaplan-Meier method,log-rank test,and multivariate analysis were used as appropriate.Results:In total,235 patients were included in this study.The MELD score was significantly higher at 1 week(11.8±3.1 vs 13.5±3.5,p<0.05)and 1 month(11.8±3.1 vs 13.2±4.6,p<0.05)than the baseline level and recovered at 3 months(11.8±3.1 vs 11.9±3.9,p>0.05).At 12 months,the MELD score was higher than the baseline level(11.8±3.1 vs 12.4±3.2,p<0.05).Patients with a recovery of the MELD score(n=151)at 3 months had a lower probability of overt and severe HE(log-rank p=0.015 and p=0.027,respectively)than those without recovery(n=84).Logistic regression analysis revealed that albumin(odds ratio[OR],0.926;95%confidence interval[CI],0.863–0.992;p=0.029)and platelet count(OR,0.993;95%CI,0.987–0.999;p=0.033)were independent predictive factors for non-recovery of the MELD score at 3 months.Conclusions:Liver function after TIPS creation showed a trend of deterioration at first,followed by recovery.Recovery of liver function at three months was associated with reduced overt and severe HE.

Quality of Life of the Patients Suffering from Chronic Liver Diseases at the University Health Center Campus of Lome

Objective: Assess the quality of life (QOL) of the patients suffering from chronic liver diseases in our service. Patients and Method: A transversal prospective study conducted at the service of hepatology and gastroenterology at the University health center Campus of Lomé from August 1, 2013 to August 31, 2014. We have used the short form 36 health survey questionnaire (SF-36). Patients of cirrhosis and hepatocellular carcinoma admitted during the said period were selected. Patients suffering from any other chronic diseases such as psychiatric or emotional troubles;linguistic or cognitive deficiencies that could hamper the dependability of the questionnaire were excluded. Results: The average age of the patients was 46 ± 12 years old with a male predominance (sex-ratio: 2.9). Our patients were distributed into 47.4% of cirrhosis and 52.6% of CHC. Those chronic liver diseases etiologies were alcoholic (57%), B viral (66%) and C viral (12.3%). The assessment of QOL showed an overall average score of 76.34 ± 21.1;a mean score of 30.4 ± 86.8 for the physical dimension and 36.5 ± 10.3 for the mental dimension. Patients with viral liver disease had poorer physical summary score (p = 0.000) and poorer mental summary score (p = 0.014) compared to alcoholic patients. Alcohol influenced the physical dimension of the patients (p = 0.000) while the mental dimension was more affected by the age of patients (p = 0.0035). Conclusion: The quality of life is altered by the patients suffering from chronic liver diseases (p = 0035) with regard to our context. This is so in particular with those identified to be viral infected.

Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis:A prospective study

To assess the vitamin D (VD) deficiency as a prognostic factor and effect of replenishment of VD on mortality in decompensated cirrhosis. METHODSPatients with decompensated liver cirrhosis were screened for serum VD levels. A total of 101 VD deficient patients (< 20 ng/mL) were randomly enrolled in two groups: Treatment group (n = 51) and control group (n = 50). Treatment group received VD treatment in the form of intramuscular cholecalciferol 300000 IU as loading dose and 800 IU/d oral as maintenance dose along with 1000 mg oral calcium supplementation. The VD level, clinical parameters and survival of both the groups were compared for 6-mo. RESULTSPrevalence of vitamin D deficiency (VDD) in decompensated CLD was 84.31%. The mean (SD) age of the patients in the treatment group (M:F: 40:11) and control group (M:F: 37:13) were 46.2 (± 14.93) years and 43.28 (± 12.53) years, respectively. Baseline mean (CI) VD (ng/mL) in control group and treatment group were 9.15 (8.35-9.94) and 9.65 (8.63-10.7), respectively. Mean (CI) serum VD level (ng/mL) at 6-mo in control group and treatment group were 9.02 (6.88-11.17) and 29 (23-35), respectively. Over the period of time the VD, calcium and phosphorus level was improved in treatment group compared to control group. There was non-significant trend seen in greater survival (69% vs 64%; P > 0.05) and longer survival (155 d vs 141 d; P > 0.05) in treatment group compared to control group. VD level had no significant association with mortality (P > 0.05). In multivariate analysis, treatment with VD supplement was found significantly (P < 0.05; adjusted hazard ratio: 0.48) associated with survival of the patients over 6-mo. CONCLUSIONVD deficiency is very common in patients of decompensated CLD. Replenishment of VD may improve survival in patients with decompensated liver cirrhosis.

Transient elastography improves detection of liver cirrhosis compared to routine screening tests

AIM:To investigate the diagnostic significance oftransient elastography(TE) in a daily routine clinical setting in comparison to clinical signs,laboratory parameters and ultrasound.METHODS:TE,ultrasound,laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine.RESULTS:Sensitivity of TE for the detection of liver cirrhosis was 90.4%,compared to 80.1% for ultrasound,58.0% for platelet count and 45.1% for cutaneous liver signs(P < 0.0001 for comparisons with histology).AUROC for TE was 0.760(95%CI:0.694-0.825).Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825(95%CI:0.768-0.882).TE correlated with laboratory parameters of cirrhosis progression like albumin(r =-0.43),prothrombin time(r =-0.44),and bilirubin(r = 0.34; P < 0.001 for each).Particularly,in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1%(P < 0.04) and 16.3%(P < 0.02),respectively.CONCLUSION:Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients:A propensity-matched analysis from the United

BACKGROUND Alcohol-associated cirrhosis(AC)contributes to significant liver-related mortality in the United States.It is known to cause immune dysfunction and coagulation abnormalities.Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019(COVID-19).The specific association between AC and COVID-19 mortality remains inconclusive,given the lack of robust clinical evi-dence from prior studies.AIM To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States.METHODS We conducted a retrospective cohort study using the National Inpatient Sample(NIS)database 2020.Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC.A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities.Primary outcomes included median length of stay,median inpatient charges,and in-hospital mortality.Secondary outcomes included a prevalence of systemic complications.RESULTS A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC.There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC(P>0.05).There was an increased prevalence of septic shock(5.7%vs 4.1%),ventricular fibrillation/ventricular flutter(0.4%vs 0%),atrial fibrillation(13.2%vs 8.8%),atrial flutter(8.7%vs 4.4%),first-degree atrioventricular nodal block(0.8%vs 0%),upper extremity venous thromboembolism(1.5%vs 0%),and variceal bleeding(3.8%vs 0%)in the AC cohort compared to the non-AC cohort(P<0.05).There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC,with an odds ratio of 0.97(95%confidence interval:0.78-1.22,P=0.85).Predictors of mortality included advanced age,cardiac arrhythmias,coagulopathy,protein-calorie malnutrition,fluid and electrolyte disorders,septic shock,and upper extremity venous thromboembolism.CONCLUSION AC does not increase mortality in patients hospitalized with COVID-19.There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

Approach to thromboelastography-based transfusion in cirrhosis:An alternative perspective on coagulation disorders

Viscoelastic tests,specifically thromboelastography and rotational thromboelastometry,are increasingly being used in the management of postoperative bleeding in surgical intensive care units(ICUs).However,life-threatening bleeds may complicate the clinical course of many patients admitted to medical ICUs,especially those with underlying liver dysfunction.Patients with cirrhosis have multiple coagulation abnormalities that can lead to bleeding or thrombotic complications.Compared to conventional coagulation tests,a comprehensive depiction of the coagulation process and point-of-care availability are advantages favoring these devices,which may aid physicians in making a rapid diagnosis and instituting early interventions.These tests may help predict bleeding and rationalize the use of blood products in these patients.

Primary biliary cirrhosis in Brunei Darussalam

BACKGROUND:Primary biliary cirrhosis(PBC)is an uncommon autoimmune cholestatic disease that predominantly affects women.Certain human leukocyte antigens(HLAs) have been reported to be associated with susceptibility for PBC.We describe the profiles of PBC in Brunei Darussalam. METHODS:All patients with PBC(n=10)were identified from our prospective databases.The HLA profiles(n=9,PBC)were compared to controls(n=65)and patients with autoimmune hepatitis(n=13,AIH). RESULTS:All patients were women with a median age of 51 years(27-83)at diagnosis.The prevalence rate of the disease was 25.6/million-population and the estimated incidence rate varied from 0 to 10.3/million-population per year.Chinese (41.15/million)and the indigenous(42.74/million)groups had higher prevalence rates compared to Malays(22.62/ million).The prevalence among female population was 54.6/ million-population.All patients were referred for abnormal liver profiles.Five patients had symptoms at presentations: jaundice(20%),fatigue(20%),arthralgia(30%)and pruritus (20%).Serum anti-mitochondrial antibody was positive in 80%of the patients.Overlap with AIH was seen in 30%.Liver biopsies(n=8)showed stage I(n=2),II(n=4)and III(n=2) fibrosis.There were no significant differences in the HLA profiles between PBC and AIH.Compared to the controls,PBC patients had significantly more HLA class I alleles specifically B7(P=0.003),Cw7(P=0.002)and Cw12(P=0.007)but not the class II alleles.At a median follow-up of 23.5 months(2 to 108), all patients were alive without evidence of disease progression. CONCLUSIONS:PBC is also a predominant female disorder in our local setting and most had mild disease.The HLA profiles of our patients were different to what have been reported.

Primary biliary cirrhosis in India

BACKGROUND: Primary biliary cirrhosis (PBC) is a rare cause of chronic liver disease in India. We analyzed the clinical, biochemical, serological and histological features of patients with PBC for over a 10-year period. METHODS: PBC was diagnosed by the presence of raised level of serum alkaline phosphatase (ALP), anti-mitochondrial antibody (AMA) positivity (1:40 dilution), and/or diagnostic liver histology. RESULTS:Fifteen female patients with mean age of 46.5±11 years were studied. Pruritis (80%) followed by jaundice (67%), skin changes (pigmentation, coarsening, xanthelesma and vitiligo) (67%) and fatigue (60%) were common symptoms. The mean duration of the symptoms was 3.5± 5.4 years (3 months to 20 years). Dryness of eyes was observed in only 2 patients. Hepatomegaly was noted in 87% of the patients and ascites at presentation in 40%. Mean levels of bilirubin and albumin at the time of diagnosis were 3.4±3.3 mg/dl and 3.5±0.8 g/dl, respectively. The level of serum ALP ranged from 54 to 2400 IU/L, with a median being 552 IU/L (2×ULN). In all the 15 patients with AMA positive, 8(53%) were also positive for either anti-nuclear or anti-smooth muscle antibodies. Two patients presented with persistently elevated SAP after an acute hepatitic illness. Liver biopsy was available in 13 patients, diagnostic of PBC Ⅱ & Ⅲ(8) and with evidence of cirrhosis (5). Associated autoimmune disorders were observed in 5 patients (33%). The mean time for follow-up was 26±21 months (1 to 87 months). In 4 deaths, 3 were due to liver related causes. CONCLUSION: PBC is a rare cause of chronic liver disease in India. PBC in India, unlike in the West, presents late, often with features of cirrhosis and decompensation.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

Function of macrophage-derived exosomes in chronic liver disease:From pathogenesis to treatment

Chronic liver disease(CLD)imposes a heavy burden on millions of people worldwide.Despite substantial research on the pathogenesis of CLD disorders,no optimal treatment is currently available for some diseases,such as liver cancer.Exosomes,which are extracellular vesicles,are composed of various cellular components.Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication,which are associated with the occurrence of disease.Furthermore,they have application potential in diagnosis and treatment by carrying diverse curative payloads.Hepatic macrophages,which are key innate immune cells,show extraordinary heterogeneity and polarization.Hence,macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases.This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential,which will provide new insights into alleviating the global pressure of CLD.

Differential hepatic features presenting in Wilson disease-associated cirrhosis and hepatitis B-associated cirrhosis

BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.