Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Hospitalizations for alcoholic liver disease during the COVID-19 pandemic increased more for women,especially young women,compared to men

BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.

Distinctive aspects of peptic ulcer disease,Dieulafoy'slesion,and Mallory-Weiss syndrome in patients withadvanced alcoholic liver disease or cirrhosis

AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC).

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales

BACKGROUND Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance.Despite a growing number of studies in this field of hepatology,a certain role of hematological indices in the course of liver disorders has not been fully elucidated,yet.AIM To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and mean platelet volume-to-platelet-ratio(MPR)in the course of alcoholic liver cirrhosis(ALC)and nonalcoholic fatty liver disease(NAFLD).METHODS One hundred forty-two patients with ALC,92 with NAFLD and 68 persons in control group were enrolled in the study.Hematological indices(NLR,PLR and MPR),indirect and direct markers of liver fibrosis(aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index,fibrosis-4,gamma-glutamyl transpeptidase to platelet ratio,procollagen Ⅰ carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,platelet-derived growth factor AB,laminin)were measured in each person.Model for end-stage liver disease(MELD)score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients.Receiver operating characteristic(ROC)curves and area under the curve(AUC)values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD.RESULTS MPR and NLR values in ALC patients were significantly higher in comparison to control group;PLR level was significantly lower.MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis.MPR,NLR and PLR correlated with MELD score.NLR level in NAFLD patients was significantly higher in comparison to controls.MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score.AUC values and proposed cut-offs for NLR,PLR and MPR in ALC patients were:0.821(>2.227),0.675(<70.445)and 0.929(>0.048),respectively.AUC values and proposed cut-offs for NLR,PLR and MPR in NAFLD group were:0.725(>2.034),0.528(>97.101)and 0.547(>0.038),respectively.CONCLUSION Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients.MPR and NLR turned out to be the most powerful parameters in ALC patients.

Incidence, risk factors and outcome of de novo tumors in liver transplant recipients focusing on alcoholic cirrhosis

Orthotopic liver transplantation(OLT) is an established life-saving procedure for alcoholic cirrhotic(AC) patients, but the incidence of de novo tumors ranges between 2.6% and 15.7% and is significantly increased in comparison with patients who undergo OLT for other etiologies. Tobacco, a known carcinogen, has been reported to be between 52% and 83.3% in AC patients before OLT. Other risk factors that contribute to the development of malignancies are dose-dependent immunosuppression, advanced age, viral infections, sun exposure, and premalignant lesions(inflammatory bowel disease, Barrett's esophagus). A significantly more frequent incidence of upper aerodigestive(UAD) tract, lung, skin, and kidney-bladder tumors has been found in OLT recipients for AC in comparison with other etiologies. Liver transplant recipients who develop de novo non-skin tumors have a decreased long-term survival rate compared with controls. This significantly lower survival rate is more evident in AC recipients who develop UAD tract or lung tumors after OLT mainly because the diagnosis is usually performed at an advanced stage. All transplant candidates, especially AC patients, should be encouraged to cease smoking and alcohol consumption in the pre- and postOLT periods, use skin protection, avoid sun exposure and over-immunosuppression, and have a yearly otopharyngolaryngeal exploration and chest computed tomography scan in order to prevent or reduce the incidence of de novo malignancies. Although still under investigation, substitution of calcineurin inhibitors for sirolimus or everolimus may reduce the incidence of de novo tumors after OLT.

Budd-Chiari like syndrome in decompensated alcoholic steatohepatitis and liver cirrhosis

A rare case of pseudo-Budd-Chiari Syndrome in a patientwith decompensated alcoholic liver disease is reported.Although clinical and radiological findings suggestedBudd-Chiari Syndrome, the liver biopsy revealedmicronodular cirrhosis and absence of histological signsof hepatic outflow obstruction.

Trends of alcoholic liver cirrhosis readmissions from 2010 to 2018:Rates and healthcare burden associated with readmissions

BACKGROUND Alcoholic liver cirrhosis(ALC)is a chronic liver disease with varying disease severity.Readmissions of ALC are associated with poor outcomes.AIM To identify and assess trends of readmissions for ALC over an eight-year period.METHODS This retrospective interrupted trend study analysed 30-d readmissions of ALC in the United States from 2010 to 2018 using the National Readmissions Database.Hospitalization for ALC was the reason for index admission obtained using the International Classification of Diseases codes(571.2 and K70.3X).Biodemographic characteristics and hospitalization trends were highlighted over time.A multivariate regression analysis model was used to calculate the trend for riskadjusted odds of 30-d all-cause ALC readmissions,ALC specific readmission rate,ALC readmission proportion,inpatient mortality,mean length of stay(LOS)and mean total hospital cost(THC)following adjustments for age,gender,grouped Charlson Comorbidity Index,insurance,mean household income,and hospital characteristics.RESULTS There was a trend towards increasing total 30-d readmissions of ALC from 7660 in 2010 to 15085 in 2018(P<0.001).Patients readmitted for ALC were noted to have an increasing comorbidity burden over time.We noted a rise in the risk-adjusted 30-d all-cause readmission of ALC from 24.9%in 2010 to 29.9%in 2018(P<0.001).ALC-specific readmission rate increased from 6.3%in 2010 to 8.4%in 2018(P<0.001)while ALC readmission proportion increased from 31.4%in 2010 to 36.3%in 2018(P<0.001).Inpatient mortality for 30-d readmissions of ALC declined from 10.5%in 2010 to 8.2%in 2018(P=0.0079).However,there was a trend towards increasing LOS from 5.6 d in 2010 to 6.3 d in 2018(P<0.001)and increasing THC from 13790 dollars in 2010 to 17150 dollars in 2018(P<0.001).The total days of hospital stay attributable to 30-d readmissions of ALC increased by 119.2%while the total attributable hospital costs increased by 149%by the end of 2018.CONCLUSION There was an increase in the 30-d readmission rate and comorbidity burden for ALC;however,inpatient mortality declined.Additionally,there was a trend towards increasing LOS and THC for these readmissions.

Randomized controlled trial of Qing Gan Huo Xue Prescription in the treatment of alcoholic liver cirrhosis

Objective:To evaluate the efficacy of Qing Gan Huo Xue Prescription(QGHXP)in the treatment of patients with alcoholic liver cirrhosis(ALC)of damp and heat stasis syndrome.Methods:A total of 69 patients with ALC were randomly divided into TCM group(n=35)and control group(n=34).The TCM group was given QGHXP 1 pack TID orally.Control group received polyene phosphatidylcholine capsule 456 mg TID for 24 weeks.The observation measurements are symptom efficacy rate,serum level of liver enzyme,and non-invasive liver cirrhosis evaluation,including liver stiffness measurement(LSM)examininged by FibroTouch,APRI score,FIB-4 index and Maddrey discriminant function.Results:The symptom efficacy rate of the experimental group and the control group was 85.70%and 61.80%(P=0.024).Liver enzyme levels(serum ALP,γ-GT,AST and ALT)of TCM group were lower than those of control group(P<0.05).LSM of TCM group was reduced after treatment,and was significant lower than control group(14.19±1.49)vs.(15.06±1.24)(P<0.05).The APRI scores,FIB-4 index and Maddrey discriminant functions of TCM group were lower than those of control group(P<0.05).Conclusion:QGHXP is an effective alternative for the treatment of damp and heat stasis syndrome of ALC in improving liver function and clinical symptoms.

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.

Alcoholic liver disease:Utility of animal models

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

Liver transplantation and alcoholic liver disease:History,controversies,and considerations

Alcohol consumption accounts for 3.8% of annual global mortality worldwide, and the majority of these deaths are due to alcoholic liver disease(ALD), mainly alcoholic cirrhosis. ALD is one of the most common indications for liver transplantation(LT). However, it remains a complicated topic on both medical and ethical grounds, as it is seen by many as a "self-inflicted disease". One of the strongest ethical arguments against LT for ALD is the probability of relapse. However, ALD remains a common indication for LT worldwide. For a patient to be placed on an LT waiting list, 6 mo of abstinence must have been achieved for most LT centers. However, this "6-mo rule" is an arbitrary threshold and has never been shown to affect survival, sobriety, or other outcomes. Recent studies have shown similar survival rates among individuals who undergo LT for ALD and those who undergo LT for other chronic causes of end-stage liver disease. There are specific factors that should be addressed when evaluating LT patients with ALD because these patients commonly have a high prevalence of multisystem alcohol-related changes. Risk factors for relapse include the presence of anxiety or depressive disorders, short pre-LT duration of sobriety, and lack of social support. Identification of risk factors and strengthening of the social support system may decrease relapse among these patients. Family counseling for LT candidates is highly encouraged to prevent alcohol consumption relapse. Relapse has been associated with unique histopathological changes, graft damage, graft loss, and even decreased survival in some studies. Research has demonstrated the importance of a multidisciplinary evaluation of LT candidates. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including 12-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Nutritional therapy helps to reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. For muscular recovery, supervised physical activity has been shown to lead to a gain in muscle mass and improvement of functional activity. Early LT for acute alcoholic hepatitis has been the subject of recent clinical studies, with encouraging results in highly selected patients. The survival rates after LT for ALD are comparable to those of patients who underwent LT for other indications. Patients that undergo LT for ALD and survive over 5 years have a higher risk of cardiorespiratory disease, cerebrovascular events, and de novo malignancy.

Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis

AIM: To assess the relationship between vitamin D re-ceptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucle-otide gene polymorphisms of the VDR were investigatedby polymerase chain reaction and restriction fragment length polymorphism: FokI C>T (F/f), BsmI A>G (B/b), ApaI T>G (A/a) and TaqI T>C (T/t) (BAT). RESULTS: The frequencies of genotypes in patients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for ApaI A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotype of BsmI and the T/T genotype of TaqI was signif icantly associated with HCC (45/160 vs 33/80, P < 0.05 and 44/160 vs 32/80, P < 0.05, respectively). The absence of the A-T-C protective allele of BAT was signif i-cantly associated with the presence of HCC (46/80 vs 68/160, P < 0.05). A strong association was observed between carriage of the BAT A-T-C and G-T-T haplotypes and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, P < 0.002, respectively).CONCLUSION: VDR genetic polymorphisms are sig-nificantly associated with the occurrence of HCC in patients with liver cirrhosis. This relationship is more specific for patients with an alcoholic etiology.

Therapy for alcoholic liver disease

Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function &#x02265; 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.

Influence of unrecorded alcohol consumption on liver cirrhosis mortality

Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans(e.g.,cosmetics containing alcohol).The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality.Compounds besides ethanol have been hypothesized as being responsible for this observation.On the other hand,chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds.However,illegally produced spirits regularly contain higher percentages of alcohol(above 45%by volume),but for considerably less costs compared with licit beverages,potentially causing more problematic patterns of drinking.In this review,it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates.Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking.It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits(e.g.,higher levels of certain contaminants in home-produced products)and liver toxicity on a population scale.Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine,which were reported to be consumed as surrogate alcohol in Russia,leading to an outbreak of acute cholestatic liver injury,histologically different from conventional alcoholic liver disease.

Alcoholic liver disease and hepatitis C:A frequently underestimated combination

Alcoholic liver disease(ALD) and hepatitis C virus(HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world.This review discusses the epidemiology and combined impact of ALD and HCV on the progres sion of liver disease.ALD and HCV affect the progres sion of liver disease to liver cirrhosis and hepatocellular carcinoma(HCC) in a synergistic manner.Thus, the risk for HCC increases f ive times with a daily alcohol con sumption of 80 g;in the presence of HCV it is increased 20fold, and a combination of both risk factors leads to a more than 100fold risk for HCC development.Alcohol consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV replication.Several molecu lar mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease progression.They include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of iron.Thus, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liversecreted systemic iron hormone hepcidin.A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the future.For now, it can be generally concluded that HCVinfect ed patients should abstain from alcohol and alcoholicsshould be encouraged to participate in detoxification programs.

Recent trends in liver transplantation for alcoholic liver disease in the United States

AIM To examine temporal changes in the indications for liver transplantation(LT) and characteristics of patients transplanted for alcoholic liver disease(ALD).METHODS We performed a retrospective cohort analysis of trends in the indication for LT using the United Network for Organ Sharing(UNOS) database between 2002 and 2015. Patients were grouped by etiology of the liver disease and characteristics were compared using χ~2 and t-tests. Time series analysis was used identifying any year with a significant change in the number of transplants per year for ALD, and before and after eras were modeled using a general linear model. Subgroup analysis of recipients with ALD was performed by age group, gender, UNOS region and etiology(alcoholic cirrhosis, alcoholic hepatitis and hepatitis C-alcoholic cirrhosis dual listing).RESULTS Of 74216 liver transplant recipients, ALD(n = 9400, 12.7%) was the third leading indication for transplant after hepatitis C and hepatocellular carcinoma. Transplants for ALD, increased from 12.8%(553) in 2002 to 16.5%(1020) in 2015. Time series analysis indicated a significant increase in the number of transplants per year for ALD in 2013(P = 0.03). There were a stable number of transplants per year between 2002 and 2012(linear coefficient 3, 95%CI:-4.6, 11.2) an increase of 177 per year between 2013 and 2015(95%CI: 119, 234). This increase was significant for all age groups except those 71-83 years old, was observed for both genders, and was incompletely explained by a decrease in transplants for hepatitis C and ALD dual listing. All UNOS regions except region 9 saw an increase in the mean number of transplants per year when comparing eras, and this increase was significant in regions 2, 3, 4, 5, 6, 8, 10 and 11.CONCLUSION There has been a dramatic increase in the number of transplants for ALD starting in 2013.

Alcoholic disease: Liver and beyond

The harmful use of alcohol is a worldwide problem. It has been estimated that alcohol abuse represents the world&#x02019;s third largest risk factor for disease and disability; it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others. Liver is the main organ responsible for metabolizing ethanol, thus it has been considered for long time the major victim of the harmful use of alcohol. Ethanol and its bioactive products, acetaldehyde-acetate, fatty acid ethanol esters, ethanol-protein adducts, have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver. A similar mechanism has been postulated for the alcohol-related pancreatic damage. Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the &#x0201c;necrosis-fibrosis&#x0201d; sequence that finally leads to atrophy and fibrosis, morphological hallmarks of alcoholic chronic pancreatitis. Even if less attention has been paid to the upper and lower gastrointestinal tract, ethanol produces harmful effects by inducing: (1) direct damaging of the mucosa of the esophagus and stomach; (2) modification of the sphincterial pressure and impairment of motility; and (3) alteration of gastric acid output. In the intestine, ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system. Notably, disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage. This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver, pancreas and gastrointestinal tract.

Alcoholic liver disease

Alcohol use disorders affect millions of individuals worldwide.Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs.Alcoholic liver disease(ALD) may take the form of acute involvement(alcoholic hepatitis)or chronic liver disease(steatosis,steatohepatitis,fibrosis and cirrhosis).The severity and prognosis of alcohol-induced liver disease depends on the amount,pattern and duration of alcohol consumption,as well as on the presence of liver inflammation,diet,nutritional status and genetic predisposition of an individual.While steatosis is an almost completely benign disease,liver cirrhosis is associated with marked morbidity,mortal-ity and life expectancy shortening.The median survival of patients with advanced cirrhosis is 1-2 years.Se-vere acute alcoholic hepatitis(AH)is associated with mortality as high as 50%.It has been managed with corticoids,pentoxifylline and enteral nutrition,although evidence based data are still conflicting.Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH.Absolute abstinence is a basic condition for any treatment of acute or chronic ALD,the other therapeutical procedure being of a supportive nature and questionable significance.Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alco-hol dependent patients.Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation,which leads to a markedly pro-longed life expectancy.The crucial step in ALD preven-tion is in the prevention of alcohol abuse,whereas the prevention of liver injury in active alcohol abusers is not clinically applicable.