Vol. 18 Issue 1
On the cover: The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver
This manuscript does not have abstract.
With the discovery of direct-acting antivirals and the prospective of viral hepatitis becoming curable, alcohol liver disease (ALD) is back to primetime. In the last 20 years, there have been many advances in the understanding of the biology, the psychology and the social and environmental factors associated with this long-known medical problem. Recent information about regional, ethnic, cultural and genetic factors seem to be relevant for the Latin American (LA) population. New approaches based on the new concepts and current information will render better results in the overall management of patients with this problem. Considering alcohol use disorder and ALD as part of the same entity managing it in a multidisciplinary approach seems to be best way to deal with this disease.
In North America, the role of Hepatologists in treatment of hepatocellular carcinoma is limited. We conducted a pilot project wherein a Hepatologist participated directly in microwave ablation of HCC at an academic center in the United States (n=14). The pilot project shows promising outcomes, with complete remission rate of 93%.
Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis worldwide. The virus is mainly transmitted via the fecaloral route and, the incidence of infection is closely related to low socioeconomic conditions and poor sanitation. Mexico, previously categorized an area of high endemicity for HAV infection, is undergoing epidemiological transition. However, a limited number of HAV-related scientific reports regarding to virus burden is available. According to the local government health agency (Secretaría de Salud, SSA in Spanish), from 1994 to 2017 a reduction in the incidence of hepatitis related to HAV has been reported. However, HAV is still the most common cause of viral hepatitis in the country, and the pediatric population is the most prone to be infected with this virus. The analysis of the SSA data reveals that most of the reported cases from 1994 to 2017 were found in highly industrialized states. This information contradicts the documented relationship between the highest prevalence of infection and the lowest socio-economic status, and supports the necessity of viral detection and notification of HAV cases. Moreover, in spite that four HAV vaccines are available in Mexico and universal vaccination has been shown to be beneficial in developing countries in terms of declining endemicity, HAV vaccination is not mandatory in Mexico. In this review, preventive strategies including appropriate diagnosis, vaccination and public health policies on the basis of the epidemiologic status of HAV in Mexico are discussed.
Introduction. Acoustic Radiation Force Impulse (ARFI) elastography evaluates hepatic fibrosis non-invasively and has been mainly validated in viral hepatitis. Data on rare liver diseases such as autoimmune hepatitis (AIH), overlap syndrome, primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) are sparse. Material and methods. 85 patients (including 31 AIH, 26 PBC, 16 PSC and 3 PSC- and 9 PBC- AIH-overlap syndromes) were retrospectively analysed pointing at ARFI elastography of the liver and the correlation with histologic Ishak fibrosis score (F0-6). Results of shear wave velocities (m/s) were expressed as mean ± standard deviation. Results. The mean shear wave velocity of all 85 patients showed 1.80 ± 0.84 m/s (0.74-3.98). The ARFI elastography values correlated with the degree of fibrosis in all patients overall and in patients with AIH, overlap syndrome and PSC, respectively. The subgroup of 26 patients with PBC (only with Ishak F ≤ 3) revealed no correlation between ARFI and these early fibrosis stages (r = 0.019, p = 0.927). ARFI elastography correlated with bilirubin, AST, but not with patient age, body mass index or measurement depth. The cut-off of 2.04 m/s for detecting cirrhosis (Ishak F ≥ 5) leads to a sensitivity of 90.0% and specificity of 74.7% (AUROC 87.2%). Conclusion. ARFI elastography can evaluate fibrosis in AIH, PSC and PSC-/PBC-AIH-overlap syndrome with good accuracy for the detection of hepatic cirrhosis. Shear wave velocities in PBC should be interpreted with caution in early stages of fibrosis.
Introduction and aim. Considered as a healthcare quality indicator, hospital readmissions in decompensated cirrhosis predispose the patients and the society to physical, social and economic distresses. Few studies involving North American cohorts have identified different predictors. The aim of this study was to determine and validate the predictors of 1-month and 3-months readmission in an Asian cohort. Material and methods. We prospectively studied 281 hospitalised patients with decompensated cirrhosis at a large tertiary care public hospital in India between August 2014 and August 2016 and followed them for 3 months. Data regarding demographic, laboratory and disease related risk factors were compiled. We used multivariate logistic regression to determine predictors of readmission at 1-month and 3-months and receiver operating curves (ROC) for significant predictors to obtain the best cut-offs. Results. 1-month and 3-months readmission rates in our study were 27.8% and 42.3%, respectively. Model for End stage Liver Disease (MELD) score at discharge (OR:1.24, p < 0.001) and serum sodium (OR:0.94, p-0.039) independently predicted 1- month and MELD score (OR:1.11, p-0.003), serum sodium (OR:0.94, p-0.027) and male gender (OR:2.19, p-0.008) independently predicted 3-months readmissions. Neither aetiology nor complications of cirrhosis emerged as risk factors. MELD score >14 at discharge and serum sodium < 133 mEq/L best predicted readmissions; MELD score being a better predictor than serum sodium (p - 0.0001). Conclusions. High rates of early and late readmissions were found in our study. Further, this study validated readmission predictors in Asian patients. Structured interventions targeting this risk factors may diminish readmissions in decompensated cirrhosis.
Introduction and aim. Matrix metalloproteinase (MMP)-2 and MMP-9 are reported to participate in several pregnancy-related diseases, including intrahepatic cholestasis of pregnancy (ICP), which is a severe liver disorder in pregnant women. Meanwhile, ample evidences have demonstrated that celastrol inhibits the activity and expression of MMPs. The present study aims to examine the effect of celastrol to alleviate symptoms of ICP in rat model. Material and methods. By inducing ICP with 17 - ethinylestradiol in pregnant female rats, we assessed the impact of celastrol administration on symptoms of ICP, such as the rate of bile flow, the level of total bile acids (TBA), and the activities of MMP-2 and -9. Furthermore, the correlations between the levels of MMPs with the examined ICP symptoms were investigated. Results. In rats with ICP, both MMP-2 and -9 exhibited significantly elevated activities, which were inhibited by the administration of celastrol. Furthermore, ICP symptoms such as bile flow rate and total TBA were restored by celastrol. Lastly, there were strong correlations between levels of the two MMPs and TBA. Conclusion. Our findings described for the first time the effects of celastrol to attenuate ICP symptoms through an inhibition of both MMP-2 and -9, providing evidence for a potential role of celastrol as a new drug for the treatment of ICP.
Introduction and aim. Acute-on-chronic liver failure (ACLF) is defined by the development of acute deterioration of liver function associated with failure of other organs and high short-term mortality in patients with chronic liver disease (CLD). There is no consensus on the diagnostic criteria, and its independence from ordinary decompensation of CLD has frequently been questioned. This study aimed to identify and characterize this condition and to test the CLIF-C OF score comparing it to the 2016-MELD (with sodium) and the Child-Pugh. Material and methods. 18-month prospective observational study with systematic inclusion of admitted patients with CLD decompensation. Results. 39 patients had ACLF (33.1%). These patients experienced higher 28-day and 90-day mortality, when compared to patients without ACLF (43.6% and 64.1% vs. 2.5% and 7.6% respectively, p < 0.0001). ACLF was linked with a higher acute infection rate (74.4%). For all patients (N = 118), the scores 2016-MELD, CLIF-C OF and Child-Pugh showed an area under the curve (AUC) for 28-day mortality of 0.908, 0.844, 0.753 and for 90-day of 0.902, 0.814, 0.724 respectively, p < 0.0001 for all scores. The 90-day mortality 2016-MELD AUC was greater than the CLIF-C OF AUC, p = 0.021. Within ACLF patients, the 2016-MELD, CLIF-C ACLF and Child-Pugh scores showed an AUC of 0.774, 0.734, 0.584 (28-day) and 0.880, 0.771, 0.603 (90-day); for 2016-MELD p = 0.004 (28-day) and p < 0.0001 (90-day). Conclusion. ACLF is a frequent and relevant condition, associated with high mortality. The CLIF-C OF score revealed good accuracy and diagnoses ACLF when it is present. However, the 2016-MELD performed better for 90-day mortality prediction.
Introduction and aim. Serum glypican-3 (GPC3) has been explored as a non-invasive biomarker of hepatocellular carcinoma (HCC). However, controversy remains on its diagnostic accuracy. Therefore, we aimed to conduct a systematic review and metaanalysis to evaluate the differential diagnostic accuracy of serum GPC3 between HCC and liver cirrhosis (LC) cases. Material and methods. After the strict filtering and screening of studies from NCBI, PUBMED, Clinical Trials, Cochrane library, Embase, Prospero and Web of Science databases, 11 studies were selected. All studies provided the sensitivity and specificity of GPC3 and the alpha-fetoprotein (AFP) in the HCC and LC diagnosis. The sensitivity and specificity, and the area under the receiver operating characteristic curve (AUC) were determined and compared between GPC3 and AFP, which was set as a positive control. Results. Pooled sensitivity (95% CI) and specificity (95% CI) were 0.55 (0.52-0.58) and 0.58 (0.54-0.61) for GPC3, 0.54 (0.51-0.57) and 0.83 (0.80-0.85) for AFP, and 0.85 (0.81-0.89) and 0.79 (0.73-0.84) for GPC3 + AFP, respectively. The AUCs of GPC3, AFP and GPC3 + AFP were 0.7793, 0.7867 and 0.9366, respectively. GPC3 had a nearly similar sensitivity as AFP, while the specificity and AUC of GPC3 was lower than that of AFP. The combination of GPC3 and AFP yielded a better sensitivity and AUC than GPC3 or AFP. Conclusion. Serum GPC3 is inferior to AFP in the differential diagnosis between HCC and LC. However, the combination of GPC3 and AFP exhibited a much better performance.
Introduction and aim. Hepatitis C virus (HCV) infection is a global medical problem. HLA –DRB1 alleles have an important role in immune response against HCV. The aim of this study is to clarify the contribution of HLA –DRB1 alleles in HCV susceptibility in a multicentre family-based study. Material and methods. A total of 162 Egyptian families were recruited in this study with a total of 951 individuals (255 with chronic hepatitis C (CHC), 588 persons in the control group(-ve household contact to HCV) and 108 persons who spontaneously cleared the virus (SVC). All subjects were genotyped for HLA -DRB1 alleles by SSP-PCR and sequence based typing (SBT) methods. Results. The carriage of alleles 3:01:01 and 13:01:01 were highly significant in CHC when compared to that of control and SVC groups [OR of 3 family = 5.1289, PC (Bonferroni correction ) = 0.0002 and 5.9847, PC = 0.0001 and OR of 13 family = 4.6860, PC = 0.0002 and OR = 6.5987, PC = 0.0001 respectively]. While DRB1*040501, DRB1*040101, DRB1*7:01:01 and DRB1*110101 alleles were more frequent in SVC group than CHC patients (OR = 0.4052, PC = 0.03, OR: OR = 0.0916, PC = 0.0006, OR = 0.1833, PC = 0.0006 and OR = 0.4061, PC = 0.0001 respectively). Conclusions. It was concluded that among the Egyptian families, HLA- DRB1*030101, and DRB1*130101 alleles associated with the risk of progression to CHC infection, while DRB1*040101, DRB1*040501, DRB1*7:01:01and DRB1*110101 act as protective alleles against HCV infection.
Introduction and aim. The association between lysosomal acid lipase (LAL) activity and liver steatosis or fibrosis is poorly studied. The aim of our study was to determine the predictive power of LAL for cryptogenic liver steatosis and cryptogenic significant fibrosis/ cirrhosis. Material and methods. Cross-sectional observational study of 101 adult patients with unexplained elevated liver enzymes/hepatomegaly with or without dyslipidemia submitted to the determination of LAL activity and LIPA gene (E8SJMC. 894G→A) mutation. Seventy-one patients underwent liver biopsy or FibroScan®. Patients with an identifiable liver dysfunction cause and well-stablished NAFLD/NASH risk factors were excluded. Predictors for liver steatosis, significant fibrosis (≥ F2) or cirrhosis (F4) were evaluated. Results. Liver steatosis and fibrosis were mainly assessed by liver biopsy (74.6%; n = 53). Steatosis was present in 62.0% (n = 44), significant fibrosis in 47.9% (n = 34) and cirrhosis in 39.4% (n = 28). The median LAL was 0.36 (0.21-0.46)nmol/spot/h (vs. 0.29 (0.20-0.47); p = 0.558) for liver steatosis, 0.22 (0.11-0.29) nmol/spot/h (vs. 0.40 (0.34-0.51); p < 0.001) for significant fibrosis and 0.21 (0.11-0.27) nmol/spot/h (vs. 0.40 (0.32-0.52); p < 0.001) for cirrhosis. No LIPA gene mutations were found. LAL activity was the strongest predictor of significant fibrosis (AUROC: 0.833; p < 0.001) with a cut-off of 0.265 (sensitivity: 85.9%; specificity: 75.0%) and cirrhosis (AUROC: 0.859; p < 0.001) with a cut-off of 0.235 (sensitivity: 86.2%; specificity: 75.0%), being higher than FIB4, GUCI or APRI. However, LAL activity was not associated with liver steatosis (AUROC: 0.536; p = 0.558). Conclusion. LAL activity can be considered a non-invasive new marker of cryptogenic liver fibrosis with higher accuracy than other known biomarkers. LAL activity < 0.265 nmol/spot/h was strongly associated with cryptogenic significant fibrosis and < 0.235 nmol/spot/h with cryptogenic cirrhosis. LAL activity was not associated with cryptogenic liver steatosis.
Introduction and aim. We developed a rat model of portal vein ligation (PVL) with venous congestion (PVL+C) to investigate beneficial effect PVL plus congestion for regeneration of intact liver segments. Materials and methods. In the PVL group, portal vein branches were ligated except the caudate lobe (CL). In the PVL + C group, the left lateral hepatic vein was ligated in addition to PVL. Chronological changes in the following variables were compared among the groups: CL weight to body weight ratio (CL/BW), embolized liver weight to body weight ratio (EL/BW), histological findings of the embolized/non-embolized liver, and expression of several mediators that affect liver regeneration in the non-embolized liver. Results. Weight regeneration of CL continued up to postoperative day (POD)7 in PVL + C, but terminated at POD2 in PVL. CL/BW at POD7 was significantly higher in PVL + C than in PVL (2.41 ≥ 0.33% vs. 1.22 ≥ 0.18%, P < 0.01). In contrast, EL/BW continued to decrease up to POD7 in PVL + C but reached nadir at POD2 in PVL. Furthermore, EL/BW at POD7 was significantly smaller in PVL + C than in PVL (0.35 ≥ 0.03% vs. 0.67 ≥ 0.08%, P < 0.01). Histologically-proven injury in the embolized liver was more severe in PVL + C than in PVL. Expression of Ki-67, IL-6, TNF-α, and HGF were greater and/or more prolonged in PVL + C than in PVL. Conclusions. Our rat model of PVL + C was considered useful for investigating the beneficial effect of congestion in addition to PVC. PVL + C caused increased devastation of the embolized liver, and higher and more prolonged expression of factors promoting liver regeneration in the non-embolized liver than in PVL.
Introduction and aim. Patients with liver cirrhosis (LC) and minimal hepatic encephalopaty have a higher accident rate. LC impairs the normal sleep-awake cycle and produces disturbances in behavior, cognition and motor skills. Abnormal melatonin (MT) levels have also been identified in LC. Administration of MT may regulate circadian rhythms and prevent the oxidative damage. We studied the effects of MT on spatial memory acquisition (SMA) and motor skills in a liver fibrosis model (LF)s. Materials and methods. Forty-five rats, divided into 4 groups. [G1: LF; G2: LF + MT; G3: MT; G4: Healthy control (HC)]. LF was induced by carbon tetrachloride intraperitoneal injection (0.2 mL/kg) for 5 months. MT was administered during 5 weeks (0.4 mg/kg/day). SMA was evaluated by using the Morris Water Maze protocol where the escape latency (EL) and mean speed were measured. Data were registered by SMART®. Results. The EL measurement analyzed by two way ANOVA: cirrhosis presented a higher EL than controls or those treated with MT suggesting impaired memory acquisition which is rescued by MT treatment. The mean speed analysis revealed that LF presented higher speed than LF+MT or HC, suggesting that LF affects motor skills, which are improved by MT. To discard whether EL is affected by altered motor skills in LF treated with MT, we compared the average EL and speed between days 2 and 6 of the training protocol. Speed was not improved during the trials unlike EL, suggesting that memory acquisition is independent of motor skills. Conclusion. These findings suggest that MT improves cognition and motor skills in the LF model.
Introduction and aim. We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients. Material and Methods. This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]). Results. No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ ritonavir combination treatment was highly effective in elderly patients. Conclusion. Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.
Introduction and aim. Patients with NASH have increased risk for sepsis or cardiovascular disease after Liver transplantation. An important role of Toll-like receptor (TLR) 4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) was demonstrated. Here, we study the role of miR-182-5p in TLR4 expression and high-fat-diet (HFD)-induced NASH in vitro and in vivo. Material and methods. Following transfection with a miR-182-5p mimic, the effect of miR-182-5p on TLR4 in RAW264.7 and HepG2 cells was investigated. Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the in vivo expression of TLR4, TNFα, and IL-6 and assessed the histologic features of the livers. Results. Following lipopolysaccharide (LPS) treatment of RAW264.7 cells, real-time RT-PCR and western blot results indicated decreases levels of TLR4 mRNA and protein in the miR-182-5p group as compared with levels observed in controls, with similar trends were observed in TNFα and IL-6 protein levels. Following oleic acid (OA) treatment of HepG2 cells, TLR4, TNFα, and IL-6 levels were significantly decreased in the miR-182-5p group as compared with levels observed in controls. Following miR-182-5p administration, TLR4 mRNA and protein levels decreased along with those of TNFα and IL-6 proteins, and the liver weight/body weight ratio of treated mice was less than that observed in controls. Furthermore, hematoxylin and eosin staining showed that the miR-182-5p-treated group exhibited low adipose cell cross-sectional areas, and Oil Red O staining showed decreases in the size of lipid droplets in the miR-182-5p-treated group. Conclusions. miR-182-5p ameliorated HFD-induced NASH by suppressing TLR4.
Introduction and aim. Studies carried out mainly in patients with hepatocellular carcinoma (HCC), have shown the prognostic significance of albumin-bilirubin (ALBI) grade. Recently, another predictive score incorporating platelet count into ALBI, PALBI grade, was introduced in patients with HCC. Aim. We evaluated the ability of ALBI and PALBI grades in predicting the outcome (mortality / liver transplantation) of patients with stable decompensated cirrhosis with various etiology of liver diseases. Material and methods. We prospectively studied 325 patients with stable decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded including albumin, bilirubin levels, platelets. We estimated ALBI and PALBI grades for every patient. Conventional prognostic scores were also evaluated; Child-Pugh (CTP), Model for End stage Liver Disease (MELD). We followed them up and recorded their outcome. Results. Beyond MELD and CTP, ALBI and PALBI grades proved significant factors associated with the outcome (HR: 2.13, 95%CI [1.59, 2.85], p < 0.001 and HR: 2.06, 95%CI [1.47, 2.9], p < 0.001, respectively), and their predictive capability was established (ROC analysis; AUC: 0.695, 95% CI [0.634, 0.755] and AUC: 0.683, 95% CI [0.621, 0.744], respectively). ALBI and PALBI performed better than CTP score (p = 0.0044 and p = 0.014, respectively). Categorization of our patients into three ALBI groups detected statistically different survival times. Accordingly, PALBI grade 3 compared to those with PALBI grade 1 and 2 patients, had worse outcome and significantly higher frequency of cirrhosis-related complications. Conclusions. ALBI and PALBI grades were validated and can be used to predict the outcome in patients with stable decompensated cirrhosis.
Introduction and aim. Interferon-free regimen has been reported to be highly efficient in treatment of HCV infection, including patients with compensated cirrhosis. We compared the efficacy of Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir and Ribavirin (OBT/PTV/r, with DSV and RBV) therapy in patients with chronic HCV genotype 1b infection and compensated cirrhosis with and without prior treatment experience with pegylated interferon and ribavirin (IFN/RBV). Material and methods. A prospective twocenter study was conducted in Mures County Hospital and Brasov County Hospital, Romania in period November 2015-July 2016. Both treatment naÏve and PegIFN/RBV experienced patients with chronic HCV genotype 1b infection received 12 weeks of OBT/ PTV/r, with DSV and RBV. Sustained virologic response 12 weeks after the treatment and eventual discontinuation of therapy due to adverse events were assessed in order to estimate safety and efficiency of therapeutic regimen. Results. Fifty nine patients were included in study, 35 (59.3%) of them were previously treated with IFN/RBV. Forty four (74.5%) patients were previously diagnosed with cirrhosis Child Pugh score 5, while 15 (25.4%) with Child Pugh score 6. All 59 patients achieved a SVR12 of 100% and one patient from treatment naÏve cohort discontinued the therapy due to hyperbilirubinemia and encephalopathy. However viral load assessed at 12 weeks after discontinuation of therapy in this patient was undetectable. Conclusion. An all-oral regimen of co-formulated OBT/PTV/r with DSV and RBV results in high rate of sustained virologic response at post-treatment week 12 among HCV GT1b infected patients associated with compensated cirrhosis, regardless of previous treatment experience with PegIFN/RBV.
Introduction and aims. Alcoholic hepatitis is the most severe manifestation of alcoholic liver disease. Unfortunately, there are still some unresolved issues in the diagnosis and management of this disease, such as the need of histological diagnosis, an accurate prognostic stratification, and the development of novel targeted therapies. The present study aimed at addressing these issues by means of metabolomics, a novel high-throughput approach useful in other liver diseases. Material and methods. 64 patients with biopsy-proven alcoholic hepatitis were included and compared with 26 patients with decompensated alcoholic cirrhosis without superimposed alcoholic hepatitis, which was ruled out by liver biopsy. Results. The comparison of the metabolic profiles of patients with alcoholic hepatitis and decompensated cirrhosis showed marked differences between both groups. Importantly, metabolic differences were found among alcoholic hepatitis patients when subjects were stratified according to 90-day survival. Based on these findings, two non-invasive signatures were developed. The first one allowed an accurate non-invasive diagnosis of alcoholic hepatitis (AUROC 0.932; 95% CI 0.901-0.963). The second signature showed a good performance in the prognostic stratification of patients with alcoholic hepatitis (AUROC 0.963; 95% CI 0.895-1.000). Conclusions. Signatures based on metabolomics allowed an accurate non-invasive diagnosis and prognostic stratification of alcoholic hepatitis. The differences observed in the metabolic profile of the patients according to the presence and severity of alcoholic hepatitis are related with different mechanisms involved in the pathophysiology of alcoholic hepatitis such as peroxisomal activity, synthesis of inflammatory mediators or oxidation. This information could be useful for the development of novel targeted therapies.
Introduction and aim. Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality, and predicting the prognosis is challenging. This study aimed to compare the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) in predicting the 90-day mortality in patients with hepatitis B virus (HBV)-associated ACLF (HBV-ACLF). Materials and methods. This prospective, observational study enrolled 54 patients with HBV-ACLF. The serum NGAL and CysC levels were determined. A multivariate logistic regression analysis was used to analyze the independent risk factors of mortality. Results. Serum NGAL, but not CysC, was found to significantly correlate with the total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD). Serum NGAL [odds ratio (OR), 1.008; 95% confidence interval (CI), 1.004-1.012; P < 0.01], but not CysC, was an independent risk factor for developing hepatorenal syndrome. Moreover, NGAL (OR, 1.005; 95% CI, 1.001-1.010; P < 0.01) along with the MELD score was independently associated with the overall survival in patients with HBV-ACLF. Patients with HBV-ACLF were stratified into two groups according to the serum NGAL level at baseline (low risk: <217.11 ng/mL and high risk: ≥ 217.11 ng/mL). The 90-day mortality rate was 22.73% (5/22) in the low-risk group and 71.88% (23/32) in the high-risk group. Moreover, NGAL, but not CysC, significantly improved the MELD score in predicting the prognosis of HBV-ACLF. Conclusion. The serum NGAL might be superior to CysC in predicting the prognosis of HBV-ACLF with the normal creatinine level.
Introduction and aim. The prevalence and incidence of chronic liver disease is increasing resulting in substantial direct and indirect medical costs. Overuse of investigations, treatments and procedures contribute to rising health care costs and can expose patients to unnecessary harm and delay in receiving care. The Choosing Wisely Canada (CWC) campaign has encouraged profesional societies to develop statements that are directly actionable by their members in an effort to promote higher-value health care that will lead to downstream effect on how other practitioners make decisions. Material and methods. The Canadian Association for the Study of the Liver (CASL) established its Choosing Wisely top five list of recommendations using the framework put forward by CWC. CASL convened a task force that developed a list of draft recommendations and shared this with CASL membership electronically with eventual ranking of the top five recommendations by consensus at Canadian Digestives Disease Week (CDDW) 2017. Following revisions, the CASL Executive Committee endorsed the final list, which was disseminated online by CWC (July 2017). Results. The top five recommendations physicians and patients should question include: 1) Don't order serum ammonia to diagnose or manage hepatic encephalopathy (HE). 2) Don't routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures. 3) Don't order HFE genotyping based on serum ferritin values alone to diagnose hereditary hemochromatosis. 4) Don't perform computed tomography (CT) or magnetic resonance imaging (MRI) routinely to monitor benign focal liver lesions. 5) Don't repeat hepatitis C viral load testing in an individual who has established chronic infection, outside of anti-viral treatment. Conclusion. The Choosing Wisely recommendations will foster patient-physician discussions, reduce unnecessary treatment and testing, avert adverse effects from testing and treatment along with reducing medical expenditure in hepatology.
Introduction and aim. Sorafenib has been the standard of care for first-line treatment of advanced hepatocellular carcinoma, a complex disease that affects an extremely heterogenous population. Thereby requiring multidisciplinary individualized treatment strategies that match the disease characteristics and the patients' specific needs. Material and methods. Data for 175 patients who received sorafenib for hepatocellular carcinoma in three different hospitals in Sao Paulo, Brazil over a span of nine years were retrospectively analyzed. Results. The median age was 62 years. Percentages of patients with Child-Pugh A, B and C liver cirrhosis were 61%, 31% and 5%, respectively. Approximately half of the patients had Barcelona Clinic Liver Cancer stage B disease, and the other half had stage C. The median treatment duration was 253 days. Sorafenib dose was reduced to 400 mg/day in 41% of the patients due to toxicity. Overall objective response rate as per Response Evaluation Criteria in Solid Tumors and its modified version was 39%. Patients who received transarterial chemoembolization (TACE) at any point during sorafenib therapy were significantly more likely to experience an objective response. After a median follow-up of 339 days, the median overall survival was 380 days. Child-Pugh cirrhosis, tumor response and concomitant chemoembolization were independent prognostic factors for overall survival in multivariate analysis. Conclusion. Our results suggest that, in experienced hands, sorafenib therapy may benefit carefully selected hepatocellular carcinoma patients for whom other therapies are initially contraindicated, including those patients with Child-Pugh B liver function and those patients who are subsequently treated with concomitant TACE.
Introduction and aim. Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has seen a rapid increase in incidence in the United States. Racial and ethnic differences in HCC incidence have been observed, with Latinos showing the greatest increase over the past four decades, highlighting a concerning health disparity. The goal of the present study was to compare the clinical features at the time of diagnosis of HCC in Latino and Caucasian patients. Material and methods. We retrospectively screened a total of 556 charts of Latino and Caucasian patients with HCC. Results. The mean age of HCC diagnosis was not significantly different between Latinos and Caucasians, but Latinos presented with higher body mass index (BMI). Rates of hypertension, diabetes, and hyperlipidemia were similar in the two groups. The most common etiology of liver disease was alcohol drinking in Latinos, and chronic hepatitis C in Caucasian patients. Non-Alcoholic Steatohepatitis (NASH) was the associated diagnosis in 8.6% of Latinos and 4.7% of Caucasians. Interestingly, alpha-fetoprotein (AFP) levels at time of diagnosis were higher in Latino patients compared to Caucasians, but this difference was evident only in male patients. Multifocal HCC was slightly more frequent in Latinos, but the two groups had similar cancerous vascular invasion. Latino patients also presented with higher rates of both ascites and hepatic encephalopathy. Conclusion. Latino and Caucasian patients with HCC present with a different profile of etiologies, but cancer features appear to be more severe in Latinos.
Introduction and aim. Wilson's disease (WD) is an uncommon cause of acute liver failure (ALF). Our aim was to describe clinical features, diagnostic findings, treatments, and outcomes of patients with ALF due to WD. Material and methods. Retrospective medical record reviews of all patients with ALF due to WD in eight years in Uruguay. Results. WD was the cause of six (15%) of thirty-nine ALF cases. All patients were females, with a mean age of 18 years. Four patients presented with hyperacute liver failure and two with acute failure. Jaundice was the main complaint of all patients. Mean total bilirubin (TB), alkaline phosphatase (AP), AST, and ALT were 27.5 mg/dL, 45.5 IU/l, 156 IU/L, and 51 IU/L, respectively. Ceruloplasmin levels were low in four patients, urinary cooper was high in four, and two had Kayser-Fleischer rings. All patients had Coombs-negative hemolytic anemia, acute kidney injury, histochemical identifiable copper, and advanced fibrosis on liver histology. The average MELD score was 36. All patients were treated with d-penicillamine and listed for urgent liver transplantation (LT). Prometheus® was performed in one patient. Three patients died: two without LT and one after LT. Three patients survived: one without LT (New Wilson Index < 11) and two with LT. The referral time to the program and the total time (referral plus waiting list time) were longer for non-survivors than for survivors (14 vs. 3 days and 23 vs. 8 respectively). Conclusion. All cases had typical clinical, analytical and histopathology characteristics. Early referral was determinant of prognosis.
Introduction and aim. Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Material and methods. A prospective cohort of adult patients with CHC treated in French general hospitals. Results. Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were ≥ 64 years old (fourth quartile) and 133 were ≥ 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.2- 92.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261, 8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. Conclusions. The high efficacy and tolerance of interferonfree regimens is confirmed in elderly patients in real-life conditions.
Introduction and aims. To determine the prevalence of minimal hepatic encephalopathy (MHE) in patients with liver cirrosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. Material and methods. We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. Results. 64 patients were included. 51.6% were male, the median age was 62years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 KPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04). Conclusion. We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.
Adenoid cystic carcinoma (ACC) is an uncommon tumor primarily occurring in the salivary glands and is relatively rare in other sites. In the liver, only one primary adenoid cystic carcinoma has been reported in the English literature. Here we presented a primary hepatic adenoid cystic carcinoma in a 44 years old male. We described its histopathologic features and its immunohistochemical profile, and reviewed the literature. The surgical treatment and patient follow up information was also presented.
IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.
Immune reconstitution syndrome is a recognized complication with initiation of highly active antiretroviral therapy for acquired immune deficiency syndrome patients co-infected with hepatitis B. Hepatitis B flares are seen in 20%-25% of patients after initiation of highly active antiretroviral therapy, an estimated 1%-5% of whom develop clinical hepatitis. We present a case of highly active antiretroviral therapy initiation for HIV that led to a flare of HBV activity despite antiviral therapy directed towards both. Liver biopsy and longitudinal serologic evaluation lend support to the hypothesis that the flare in activity was representative of IRIS. Importantly, we document eAg/eAb seroconversion with the IRIS phenomenon.
HVH (hepatic vascular hamartoma) is a tumor like malformation arising from the vascular tissue of the liver. HVH has been previously reported in animals and presents distintive features from the most frequent benign tumor like malformation of the liver, the hepatic mesenchymal hamartoma (HMH). Herein we report a case of HVH localized in hepatic segment 4b, involving the gastro hepatic ligament, successfully treated with total excision. We describe the anatomo-pathologic findings focusing on the clinical and radiological presentation, the intraoperative characteristics and the differential diagnosis.
Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dyslipidemia, and cardiovascular complications. Lack of awareness on diagnosis of this condition may hamper specific treatment, which consists on enzymatic replacement. It may prevent the progression of liver disease and its complications. We describe the case of a 53-year-old Brazilian man who was referred to our center due to the diagnosis of liver cirrhosis of unknown etiology. He was asymptomatic and had normal body mass index. He had dyslipidemia, and family history of myocardial infarction and stroke. Abdominal imaging tests showed liver cirrhosis features and the presence of intrahepatic calcifications. Initial investigation of the etiology of the liver disease was not elucidated, but liver biopsy showed microgoticular steatosis and cholesterol esters deposits in Kuppfer cells. The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).
Nowadays, the retreatment of patients with Hepatitis C virus (HCV) genotype 3 (GT3) especially cirrhotic, who have already been treated with regimens containing a NS5A inhibitor represents a challenge. Use a novel retreatment option for patients with a difficult approach. We present three case reports of retreatment with a new combination of Direct-acting antivirals (DAAs), Sofosbuvir, Elbasvir/ Grazoprevir in patients with GT3 with a previous failure with Sofosbuvir/Ledipasvir. All the cases achieved sustained virologic response (SVR) at week +12 without adverse effects. In our experience, this combo may represent an effective and safe option for these patients.
Gallbladder duplication can present a clinical challenge primarily due to difficulties with diagnosis and identification. Recognition of this anomaly and its various types is important since it can complicate a gallbladder disease or a simple hepatobiliary surgical procedure. The case report of a 63-year-old woman who presented with cholangitis and underwent a successful laparoscopic management of symptomatic gallbladder duplication is described, emphasizing several important considerations. Using ERCP, MRCP and 3D reconstructions the two cystic ducts with one common bile duct were identified. A review of the literature in referral of this variant, its anatomical classifications and significance to clinical and surgical practice is included. In conclusion, gallbladder anomalies should be anticipated in the presence of a cystic lesion reported around the gallbladder when evaluating radiologic studies. In case of surgery, preoperative diagnosis is essential to prevent possible biliary injuries or reoperation if accessory gallbladder has been overlooked during initial surgery. Laparoscopic cholecystectomy remains feasible for intervention can be safely done and awareness is necessary to avoid complications or multiple procedures.
Budd-Chiari syndrome (BCS) is a heterogeneous group of disorders characterized by hepatic venous outflow obstruction. Abernethy malformation is a congenital vascular malformation defined by diversion of portal blood away from the liver. Both conditions are rare vascular diseases. We report here the first case of a patient with combined type II Abernethy malformation and and BCS from China. The inferior vena cava obstruction was treated with percutaneous balloon angioplasty; close follow-up was elected for the Abernethy malformation.
Parastomal variceal bleeding (PVB) is a serious complication occurring in up to 27% of patients with an ostomy and concurrent cirrosis and portal hypertension. The management of PVB is difficult and there are no clear guidelines on this matter. Transjugular intrahepatic portosystemic shunt (TIPS), sclerotherapy, and /or coil embolization are all therapies that have been shown to successfully manage PVB. We present a case series with five different patients who had a PVB at our institution. The aim of this case series is to report our experience on the management of this infrequently reported but serious condition. We also conducted a systemic literatura review focusing on the treatment modalities of 163 patients with parastomal variceal bleeds. In our series, patient 1 had embolization and sclerotherapy without control of bleed and expired on the day of intervention due to hemorrhagic shock. Patient 2 had TIPS in conjunction with embolization and sclerotherapy and had no instance of rebleed 441 days after therapy. Patient 3 did not undergo any intervention due to high risk for morbidity and mortality, the bleed self-resolved and there was no further rebleed, this same patient died of sepsis 73 days later. Patient 4 had embolization and sclerotherapy and had no instance of rebleed 290 days after therapy. Patient 5 had TIPS procedure and was discharged five days post procedure without rebleed, patient has since been lost to follow-up.
Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis and is restricted to Latin America. It normally affects lungs, skin and lymph nodes. Abdominal organs are usually not involved. In rare cases paracoccidioidomycosis may simulate neoplasm. Herein we describe our experience with four cases of paracoccidioidomycosis mimicking cholangiocarcinoma. To the best of our knowledge, this is the largest case series on this subject produced in English. Paracoccidioidomycosis must be considered as a differential diagnosis of cholangiocarcinoma, especially in individuals who come from endemic areas.
Systemic symptoms such as fever and fatigue are non-specific manifestations spanning from inflammation to neoplasia. Here we report the case of a 34 year-old man who presented with systemic symptoms for four months. CT-scan and MRI revealed a 3.4 cm arterialized hepatic lesion and a 7 cm paraduodenal mass. Surgical resection of both lesions and histological examination revealed an inflammatory hepatocellular adenoma and a unicentric plasma cell type of Castleman disease. Moreover, a diffuse AA amyloid deposition in the liver was observed. Resection of both lesions was associated with an improvement of the symptoms. To our knowledge, this is the first report of a synchronous presentation of a unicentric plasma cell type of Castleman disease, inflammatory hepatocellular adenoma and AA amyloidosis.
Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has emerged as an alternative for patients with bilobar colorectal liver metastasis deemed unresectable due to inadequate future remnant liver (FRL). Nevertheless, high morbidity and mortality rates have been reported. In this setting, including hepatobiliary scintigraphy in the clinical and surgical management of patients offered ALPPS has been advocated to both assess eligibility for ALPPS stage1 and suitable time for ALPPS stage2. Recently, it was stated that partial ALPPS with a liver split restricted to 50% of the transection line (or up to the middle hepatic vein in case of right extended hepatectomy) and a shortened stage1 allows improving the postoperative course without precluding the inter-stages FRL hypertrophy. We describe a case series of p-ALPPS with stage1 performed laparoscopically, including sequential assessments of the FRL volumes and functions via pre-stage1 and pre-stage2 computed tomography volumetry and HIDA SPECT-scintigraphy. In five patients, laparoscopic p-ALPPS was associated with rapid and significant gain of remnant functional volume - much better than previously observed for ALPPS - facilitating early stage2 without inflammatory adherences. In conclusion, laparoscopic p-ALPPS is feasible and seems less aggressive than the original ALPPS technique with total transection. It may be an interesting alternative to the classical portal vein embolization (PVE) and two-stage hepatectomy strategy.
Neurological symptoms can be one of the over-riding symptoms in patients with liver cirrhosis. Patients can present with subtle changes in mood or neurological function due to hepatic encephalopathy (HE), to more severe presentations including stupor and coma. While HE, in its severe form, can be clinically easy to diagnose, more subtle forms may be more difficult to recognize. Other neurological diseases may indeed be overlooked in the context of cirrhosis or confuse the physician regarding the diagnosis. Chronic acquired hepatocerebral degeneration (CAHD) is an uncommon problem occurring in patients with cirrhosis characterised by a Parkinsonian- like neurological presentation with damage to the brain secondary to manganese (Mn) deposition. Here we describe a case of a patient with a neurological presentation of liver disease with a review of the current CAHD literature. In conclusion, CAHD is a rare condition occurring in liver cirrhosis that should always be considered in patients with neurological manifestations of chronic liver disease.