Casual finding in colonoscopy: Diphyllobothrium latum.

Diphyllobothrium spp., also known as fish tapeworms, is the largest human tapeworm, reaching up to 25 meters of length. Human are considered the definitive host in the Diphyllobothrium lifecycle. Adult tapeworms attach to human intestinal mucosa with to bilateral grooves. There are at least 14 different species of Diphyllobothrium spp. Capable of causing Dyphyllobothriosis, being D. latum and D. nihonkaiense the most frequent etiologic agents in humans. We present the clinical picture and endoscopic images on a patient with incidental finding of Dyphyllobothriosis in a colonoscopy.

Active alcohol consumption is associated with acute-on-chronic liver failure in Hispanic patients.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America. METHODS: Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models. RESULTS: We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001). CONCLUSIONS: Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF.

Implementation of a re-linkage to care strategy in patients with chronic hepatitis C who were lost to follow-up in Latin America.

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

Hepatobiliary manifestations in inflammatory bowel disease: A practical approach.

Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders. They can occur at any moment in the course of the disease or associated with the treatment. The prevalence of liver dysfunction can reach up to 50% in different studies. Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD, while primary sclerosing cholangitis is the most specific. Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists. The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD, associated diseases or to the therapies used.

Drug-Induced Liver Injury Used in the Treatment of Inflammatory Bowel Disease.

Therapeutic options for the management of inflammatory bowel disease [IBD] have been expanding in recent decades. New biological and small molecule therapies have been incorporated into the pharmacological arsenal, allowing a more personalized management, and seeking increasingly strict remission goals. However, the fear of developing adverse events represents one of the most important limitations in deciding its use by patients and by a multidisciplinary team. Despite the risk of hepatotoxicity of thiopurines and methotrexate, these drugs are still used either as monotherapy or as combined therapy with anti-tumour necrosis factor [anti-TNF] biological agents. Although drug-induced liver injury [DILI] appears to be less frequent with anti-TNF agents, newer biologics and small molecules, liver tests should be considered in the follow-up of these patients, especially regarding future combined therapy of biologics or of these drugs with small molecules. The objective of this review is to show data on the risk of developing DILI in patients with IBD who are undergoing treatment with traditional therapy or new drugs, whether biological or small molecules.

Rectal colonization by resistant bacteria increases the risk of infection by the colonizing strain in critically ill patients with cirrhosis.

BACKGROUND & AIMS: It remains unclear whether rectal colonization with multidrug-resistant organisms (MDROs) is prevalent and predisposes to infections by the same pathogens in patients with cirrhosis. METHODS: Two series of critically ill patients were evaluated. In the Barcelona cohort, 486 consecutive patients were prospectively evaluated, 129 with and 357 without cirrhosis (2015-2016). Rectal swabs were performed at admission and weekly thereafter (until intensive care unit [ICU] discharge) to detect MDRO colonization. Risk factors for colonization and infection by MDROs were evaluated. A retrospective cohort from Frankfurt (421 patients with cirrhosis; 2010-2018) was investigated to evaluate MDRO rectal colonization in another epidemiological scenario. RESULTS: In the Barcelona cohort, 159 patients were colonized by MDROs (32.7%), 102 (64.2%) at admission and 57 (35.8%) during follow-up. Patients with cirrhosis showed higher rates of rectal colonization at admission than those without cirrhosis (28.7% vs. 18.2%, p = 0.01) but similar colonization rates during ICU stay. Extended-spectrum beta-lactamase-Enterobacterales were the most frequent MDROs isolated in both groups. Colonization by MDROs independently increased the risk of infection by MDROs at admission and during follow-up. Risk of new infection by the colonizing strain was also significantly increased in patients with (hazard ratio [HR] 7.41) and without (HR 5.65) cirrhosis. Rectal colonization by MDROs was also highly prevalent in Frankfurt (n = 198; 47%; 131 at admission [66.2%] and 67 [33.8%] during follow-up), with vancomycin-resistant enterococci being the most frequent colonizing organism. Rectal colonization by MDROs was also associated with an increased risk of infection by MDROs in this cohort. Infections occurring in MDR carriers were mainly caused by the colonizing strain. CONCLUSION: Rectal colonization by MDROs is extremely frequent in critically ill patients with cirrhosis. Colonization increases the risk of infection by the colonizing resistant strain. LAY SUMMARY: Rectal colonization by multidrug-resistant organisms (MDROs) is a prevalent problem in patients with cirrhosis requiring critical care. The pattern of colonizing bacteria is heterogeneous with relevant differences between centers. Colonization by MDROs is associated with increased risk of infection by the colonizing bacteria in the short term. This finding suggests that colonization data could be used to guide empirical antibiotic therapy and de-escalation policies in patients with cirrhosis.

Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures. METHODS: We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses. RESULTS: We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates. CONCLUSIONS: The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.

Hepatitis crónica por virus C: evaluación de los pacientes tratados con antivirales de acción directa en el sistema público de Chile / Evaluation of patients with virus C hepatitis treated with direct-acting antivirals in the Chilean public system

Background Direct-acting antivirals (DAA) allowed a radical change in the treatment of hepatitis C virus (HCV), achieving the elimination of the virus or sustained viral response (SVR) in > 95% of patients, with good tolerance and few adverse effects. Aim To characterize the treated population and evaluate the efficacy of DAA treatment in the Chilean public health system. Material and Methods: Retrospective analysis of data sheets of pa- tients with chronic HCV infection collected by the Ministry of Health of Chile between 2016 and May 2019. Results Two hundred and fifty-five patients with a mean age of 59 years (51% males) were collected. Genotype 1b was predominant, 72% patients had a diagnosis of cirrhosis at the beginning of treatment. Sofosbuvir-Velpatasvir was predominantly used in 56%. SVR was achieved in 92% of cases, only 4% persisted with detectable load at 24 weeks. A significant decrease in alanine aminotransferase values (88 and 31 U/L respectively, p < 0.01) and a significant increase in plasma albumin (3.7 and 3.9 mg/dl respectively, p = 0.02) were observed. The comparative analysis of MELD-Na before and after treatment did not show a signifi- cant variation (10.8 and 10.4 respectively, p = 0.34). Conclusions These patients treated with DAAs presented SVR rates comparable with national and international data.

Frailty and reduced gait speed are independently related to mortality of cirrhotic patients in long-term follow-up.

INTRODUCTION AND OBJECTIVES: Frailty is characterized by a poor restoration of homeostasis after a stressor event. Although it is not usually diagnosed, it has been associated with decreased survival in cirrhotic patients. We aimed to evaluate the impact of frailty and decreased gait speed over survival in cirrhotic patients at long-term follow-up. MATERIALS AND METHODS: We included stable cirrhotic patients Child-Pugh B-C or MELD ≥12, ≥50 years old. We performed a clinical evaluation, anthropometry, and laboratory tests. Frailty was diagnosed using Fried Frailty Index. We evaluated survival at a 4-year follow-up. RESULTS: We included 126 patients; mean age 64±8.3 years, median MELD-Na 15[12-17], median follow-up was 881 [349-1277] days. The main etiology was MAFLD (31.4%). Frailty was diagnosed in 65.1% of patients. There were no significant differences in baseline characteristics per frailty condition. Mortality was higher in frail patients than non-frail patients (68.2% versus 20.6% at 48 months, respectively; p-value <0.001). The mean gait speed in frail and non-frail patients was 0.86±0.3m/s and 1.16±0.2m/s, respectively (p-value <0.001). Interestingly, 26.9% of patients presented a reduced gait speed (≤0.8m/s). Patients with decreased gait speed also had higher mortality than patients with normal gait speed (79.9% versus 40.8%, respectively; p-value <0.001). A multivariate-adjusted model showed that decreased gait speed (HR=3.27, 95%CI:1.74-6.14; p<0.001) and frailty (HR=4.24, 95%CI:1.89-9.51; p<0.001) were associated with mortality. CONCLUSIONS: Frailty is independently associated with decreased survival at long-term follow-up. Reduced gait speed is strongly associated with mortality and could be a surrogate marker of frailty in clinical practice.

Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF).

INTRODUCTION: The presence of hyperkalemia in different clinical scenarios has been described as a risk factor for mortality. Information about this electrolyte disorder in patients with cirrhosis is limited and there are no data in patients with acute-on-chronic liver failure (ACLF). AIM: The aim of this study was to investigate whether hyperkalemia is a risk factor for mortality in patients with cirrhosis and acute decompensation (AD) with and without ACLF. METHODS: We performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,314 consecutive patients admitted to 29 European centers with AD both with and without associated ACLF (294 and 1020 respectively). Hyperkalemia was defined as serum potassium ≥ 5.0 mEq/L. All patients had at least one valid measure of serum potassium from admission and/or through the whole hospitalization. RESULTS: 1314 patients were admitted with AD and 294 of them had ACLF at admission. Prevalence of hyperkalemia was significantly higher in ACLF versus AD (22.4% and 8.6% respectively, p<0.001). Hyperkalemia was associated with an increased 90, 180 and 360-day mortality risk in ACLF compared to AD (HR 10 vs 2.3 at 90-day p<0.001, 8.9 vs 3.1 at 180-day, p<0.001 and 5.8 vs 3.8 at 360-day, p<0.001). In a multivariate analysis, the presence of hyperkalemia during admission was independently associated with 90-day mortality [HR 2.4 (1.7 - 3.4)]. Variability of potassium between two valid measures ≥ 0.9 mg/dl was always also associated with a higher mortality rate. Addition of hyperkalemia to MELD score (MELD-K model) improved the accuracy to predict 90-day mortality risk. CONCLUSIONS: Hyperkalemia is an independent risk factor of mortality in patients with AD and ACLF. Addition of hyperkalemia to the MELD score improves diagnostic accuracy to predict 90-day mortality in patients with AD and ACLF.

Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis.

BACKGROUND & AIMS: Myeloproliferative neoplasms (MPNs) are the most frequent cause of non-tumoural non-cirrhotic splanchnic vein thrombosis (NC-SVT). Diagnosis of MPN is based on blood cell count alterations, bone marrow histology, and detection of specific gene mutations. Next-generation sequencing (NGS) allows the simultaneous evaluation of multiple genes implicated in myeloid clonal pathology. The aim of this study was to evaluate the potential role of NGS in elucidating the aetiology of NC-SVT. METHODS: DNA samples from 80 patients (75 with idiopathic or exclusively local factor [Idiop/loc-NC-SVT] and 5 with MPN and NC-SVT [SVT-MPN] negative for Janus kinase 2 gene [JAK2] [V617F and exon 12], calreticulin gene [CALR], and thrombopoietin gene [MPL] mutations by classic techniques) were analysed by NGS. Mutations involved in myeloid disorders different from JAK2, CALR, and MPL genes were categorised as high-molecular-risk (HMR) variants or variants of unknown significance. RESULTS: In 2/5 triple-negative SVT-MPN cases (40%), a mutation in exon 12 of JAK2 was identified. JAK2-exon 12 mutation was also identified in 1/75 patients with Idiop/loc-NC-SVT. Moreover, 28/74 (37.8%) of the remaining Idiop/loc-NC-SVT had at least 1 HMR variant. Sixty-two patients with Idiop/loc-NC-SVT were not receiving long-term anticoagulation and 5 of them (8.1%) had recurrent NC-SVT. This cumulative incidence was significantly higher in patients with HMR variants than in those without. CONCLUSIONS: NGS identified JAK2-exon12 mutations not previously detected by conventional techniques. In addition, NGS detected HMR variants in approximately one-third of patients with Idiop/loc-NC-SVT. These patients seem to have a higher risk of splanchnic rethrombosis. NGS might be a useful diagnostic tool in NC-SVT. LAY SUMMARY: Next-generation sequencing (NGS) performs massive sequencing of DNA allowing the simultaneous evaluation of multiple genes even at very low mutational levels. Application of this technique in a cohort of patients with non-cirrhotic non-tumoral portal vein thrombosis (NC-SVT) and a negative study for thrombophilic disorders was able to identify patients with a mutation in exon 12 not previously detected by conventional techniques. Moreover, NGS detected High Molecular Risk (HMR)-variants (Mutations involved in myeloid disorders different from JAK2, CALR and MPL genes) in approximately one third of patients. These patients appear to be at increased risk of rethrombosis. All these findings supports NGS as a potential useful tool in the management of NC-SVT.

Análisis del sistema de alistamiento y priorización para trasplante hepático de adultos en Chile

Background: In Chile, organ allocation for liver transplantation (LT) in adults is prioritized according to the MELD-Na score. Exceptions such as Hepatocellular Carcinoma (HCC) and other non-HCC exceptions receive a score called Operational MELD score. Aim: To evaluate the effectiveness of the MELD-Na score and the operational MELD score as a prioritization system for LT in Chile. Material and Methods: Retrospective analysis of the waiting list (WL) of adult candidates (≥ 15 years) for elective LT in Chile from 2011 to 2017. The probability of leaving the WL, defined by death or contraindication for LT was compared in three groups: 1) Cirrhotic patients prioritized according to their real MELD-Na score (CPM), 2) HCC and 3) other non-HCC exceptions. Results: We analyzed 730 candidates for LT, with a median age of 57 years, 431 (56%) were men. In the study period, 352 LT were performed (48%). The annual exit rate was significantly higher in the CPM group (45.5%) compared to HCC (33.1%) and non-HCC (29.3%), (p < 0.001). Post LT survival was 86% at 1 year and 85% at 5 years, without significant differences between groups. In the CPM group, post-transplant survival was significantly lower (p < 0.05) in patients with MELD-Na ≥ 30 at transplant (81% per year) compared to patients with patients with MELD-Na < 30 (91% per year). Conclusions: MELD-Na score can discriminate very well patients who have a higher risk of death in the short and medium term. However, the assignment of operational scores for situations of exception produces inequities in the allocation of organs for LT and must therefore be carefully adjusted.

[Analysis of the organ allocation system for liver transplantation in Chile]. / Análisis del sistema de alistamiento y priorización para trasplante hepático de adultos en Chile.

BACKGROUND: In Chile, organ allocation for liver transplantation (LT) in adults is prioritized according to the MELD-Na score. Exceptions such as Hepatocellular Carcinoma (HCC) and other non-HCC exceptions receive a score called Operational MELD score. AIM: To evaluate the effectiveness of the MELD-Na score and the operational MELD score as a prioritization system for LT in Chile. MATERIAL AND METHODS: Retrospective analysis of the waiting list (WL) of adult candidates (≥ 15 years) for elective LT in Chile from 2011 to 2017. The probability of leaving the WL, defined by death or contraindication for LT was compared in three groups: 1) Cirrhotic patients prioritized according to their real MELD-Na score (CPM), 2) HCC and 3) other non-HCC exceptions. RESULTS: We analyzed 730 candidates for LT, with a median age of 57 years, 431 (56%) were men. In the study period, 352 LT were performed (48%). The annual exit rate was significantly higher in the CPM group (45.5%) compared to HCC (33.1%) and non-HCC (29.3%), (p < 0.001). Post LT survival was 86% at 1 year and 85% at 5 years, without significant differences between groups. In the CPM group, post-transplant survival was significantly lower (p < 0.05) in patients with MELD-Na ≥ 30 at transplant (81% per year) compared to patients with patients with MELD-Na < 30 (91% per year). CONCLUSIONS: MELD-Na score can discriminate very well patients who have a higher risk of death in the short and medium term. However, the assignment of operational scores for situations of exception produces inequities in the allocation of organs for LT and must therefore be carefully adjusted.

[Syphilitic hepatitis. Report of three cases]. / Hepatitis sifilítica: reporte de una serie de casos.

Liver involvement occurs in 0.2 to 3% of patients with syphilis. We report three patients with liver involvement in syphilis. A 52-year-old male presenting with erythema and malaise. Laboratory showed a gamma glutamyl transpeptidase (GGT) of 853 u/l, alkaline phosphatases of 1,010 U/L and VDRL was positive. Treatment with penicillin resolved the skin problem and normalized liver enzymes. A HIV positive 30-year-old male in peritoneal dialysis presenting with itching, malaise and markedly elevated GGT and alkaline phosphatases. VDRL was positive. He was treated with penicillin with remission of symptoms and enzyme normalization. A 43-year-old male presenting with erythema, malaise, arthralgias and elevated GGT and alkaline phosphatases. VDRL was positive and treatment with penicillin reverted symptoms and laboratory abnormalities.

Hepatitis sifilítica: reporte de una serie de casos / Syphilitic hepatitis: report of three cases

Liver involvement occurs in 0.2 to 3% of patients with syphilis. We report three patients with liver involvement in syphilis. A 52-year-old male presenting with erythema and malaise. Laboratory showed a gamma glutamyl transpeptidase (GGT) of 853 u/l, alkaline phosphatases of 1,010 U/L and VDRL was positive. Treatment with penicillin resolved the skin problem and normalized liver enzymes. A HIV positive 30-year-old male in peritoneal dialysis presenting with itching, malaise and markedly elevated GGT and alkaline phosphatases. VDRL was positive. He was treated with penicillin with remission of symptoms and enzyme normalization. A 43-year-old male presenting with erythema, malaise, arthralgias and elevated GGT and alkaline phosphatases. VDRL was positive and treatment with penicillin reverted symptoms and laboratory abnormalities.