Annals of hepatology最新文献

Introduction and Objectives

In Peru the tuberculosis (TB) is an endemic infectious disease. This disease is a serious opportunistic infection in transplant recipients (LTRs) and has 20 to 74-fold increase in a chance of developing compared to the general population The prevalence of TB in (LTRs) is variable between regions. This study aims to describe the rate, clinics characteristics and mortality of TB in LTRs from a high-prevalence area.

Materials and Methods

We conducted a retrospective review of liver transplant recipients with tuberculosis diagnoses at Guillermo Almenara Hospital between Mach 2001 and March 2022.

Results

A total of 294 patients underwent LT during this period. 7 (2.3 %) adult patients were diagnosed with active TB. Mean age was 49 (32- 64) years; 5 (70 %) were males. Time interval from LT to TB diagnosis was 57 months (2-136) and 42 % had early tuberculosis (< 12 m). Three patients had disseminated TB and Four pulmonary involvement. 72 % received individualized treatment to avoid hepatotoxicity related to treatment, 28.5% had DILI with standard treatment. We found 28.5 % mortality no related to TB infections.

Conclusions

We observed a low rate of TB in LTRs (2.3%) from a high prevalence region. Most of our patients received individualized treatment.

Introduction and Objectives

The WHO proposed to eliminate viral hepatitis by the year 2030. To achieve this ambitious goal, we must evaluate the seroprevalence of these infections in different populations. This study aimed to estimate the seroprevalence of hepatitis B (HBV) and C (HCV) among pregnant women and mother-to-child transmission in a maternal hospital.

Materials and Methods

We conducted an observational, prospective and consecutive study including pregnant women from San Isidro Maternal and Children Hospital whose births occurred between 05/01/2019 and 04/30/2021. In all patients HBsAg and anti-HCV were assessed during the 1st and 3rd trimester of pregnancy together with HIV. In the case of presenting HBsAg+, anti-HBcIgG was performed on the same sample followed by HBV-DNA PCR. In the case of presenting anti-HCV+, a confirmatory test was performed with PCR HCV-RNA. Neonates of HBsAg+ or HCV+ were follow-up for 3 years.

Results

2762 births were included during the period under study. Five (0.18%) HBsAg+ pregnant women were identified, median age was 25 years (range 17-36), of which only 1 had anti-HBcIgG+. Given the suspicion of chronic HBV and the delay in obtaining the HBV-DNA results, treatment with tenofovir was started. In successive controls, no chronic HBV infection was diagnosed in neonates. Anti-HCV+ was detected in 8 (0.29%) patients, with a median age of 29 years (range 19-38 years), of which only one patient presented detectable HCV-RNA, genotype 4. This patient had a diagnosis of HCV chronic prior to pregnancy and her son presented anti-HCV- at age 3. Finally, one patient with HBsAg+ and another with anti-HCV+, but negative viral loads presented HIV+.

Conclusions

The gestation period is an excellent opportunity to carry out health checks. During the studied period, the seroprevalence of HBsAg+ and anti-HCV+ was very low. These types of interventions are essential to achieve the objectives set by the WHO.

Introduction and Objectives

Acute-on-chronic liver failure (ACLF) in cirrhotic patients is characterized by acute deterioration of liver function and severe organ injury with high short-term mortality. Liver transplantation is the only treatment to improve survival. A pilot study suggested that plasma exchange with human serum albumin 5% (PEA5%) as a replacement fluid is feasible and safe in ACLF patients and may improve organ function and survival. This study aimed to assess PE-A5% as a treatment for patients with ACLF in a pivotal study.

Materials and Methods

A phase 3, multicenter, randomized (1:1), controlled, parallel-group, open-label study (APACHE) compares standard medical treatment (SMT) + PE-A5% (treatment arm) to SMT alone (control arm). PE-A5% is performed using Albutein 5% (Grifols). Treatment schedule consists of two initial PE-A5% sessions on consecutive days followed by every other day PE-A5% (min-max 4-9 PE-A5%). Patients receive IVIG (200mg/kg) after every 2 PE-A5% to prevent hypogammaglobulinemia-associated infections, and FFP after each PE-A5% to prevent coagulopathy. Eligible patients are adult (18-79 years old), with ACLF-1b, ACLF-2, or ACLF-3a at admission or during hospitalization. Main exclusion criteria are patients with ACLF-1a or ACLF-3b, ACLF >10 days before randomization, septic shock requiring norepinephrine (>0.3µg/kg/min) or a second vasopressor, active infection, and severe respiratory failure.

Results

Target enrollment is 380 ACLF patients at high risk of hospital mortality. The primary efficacy endpoint is the 90-day overall survival. Secondary efficacy endpoints include 90-day transplant-free survival and 28-day overall survival. Main exploratory endpoints include overall and transplant-free survival at days 28 and 90, in-patient hospital and ICU stay, incidence of organ failures and ACLF course. Safety analyses include adverse events, vital signs, physical assessments, and laboratory tests.

Conclusions

APACHE will provide pivotal results on the efficacy and safety of PE-A5% as a treatment to improve survival in ACLF (NCT03702920;EudraCT:2016-001787-10).

Introduction and Objectives

The pathophysiology of NAFLD is only partially unrevealed; it is considered as a multifactorial disorder, attributed to multiple, parallel “hits,” both genetic and environmental. It has been described that the single nucleotide polymorphism at rs738409 in the PNPLA3 gene is strongly associated with hepatic steatosis and its progression. Conversely, H. pylori infection has been related to metabolic syndrome, type-2 diabetes mellitus, and dyslipidemia, which are known risk factors for NAFLD. However, the evaluation of Infection and the rs738409 polymorphism in the PNPLA3 gene has not been explored.

Materials and Methods

this is a preliminary report of a prospective multicenter study from December 2020 to June 2021 in northeastern Argentina. 76 dyspeptic adult patients who fulfilled the ROME-IV criteria and underwent gastroscopy, of which 69 were included. The presence of H. pylori was determined by gastric histology. Biochemical and clinical parameters were recorded. NAFLD was defined by liver ultrasonography. The PNPLA3 gene was analyzed by PCR-RFLP in rs738409.

Results

The prevalence of NAFLD was 45% (31/69), with Hpyl+ 48% (17/36) and Hpyl- 42% (14/33) (p: ns). The variables significantly associated with NAFLD were BMI, dyslipidemia, Diabetes/prediabetes, presence of the G allele of PNPLA3, and the GG genotype. In the multivariate analysis, BMI (OR 1.63 95%CI 1.22-2.19) and the G-allele of PNPLA3 (OR 7.35 95%CI 1.34-40) were independently associated with NAFLD. When subjects with NAFLD were analyzed, the interaction between Hpyl and PNPLA3 allele-G was significantly associated with NAFLD (65%) and increased risk of liver fibrosis (FIB-4 > 1.3 41%).

Conclusions

the presence of NAFLD was associated with BMI and G-allele of PNPLA3. The combination of Hpyl infection and the G-allele of PNPLA3 were associated with NAFLD and risk of fibrosis (FIB-4)

Introduction and Objectives

Little is known about current practice of liver transplantation (LT) in Latin American countries (LATAM). This study aimed to describe LT activity, immunosuppression protocols and policies regarding prophylaxis of cytomegalovirus (CMV) infection and hepatitis B virus (HBV) recurrence in different active LATAM centers.

Materials and Methods

A web-based survey with 20 questions regarding LT practice was sent to all members of ALEH LT SIG in December 2022.

Results

22 centers performing 35 [5-160] LT per year from Brazil (n=5), Argentina (n=4), Chile (n=4), Ecuador (n-2), Mexico (n=2), Colombia (n=1), Costa Rica (n=1), Peru (n=1), Dominican Republic (n=1) and Uruguay (n=1) answered the survey. Tacrolimus, mycophenolate and prednisone was the main immunosuppressive regimen employed by most (72%) centers and 81% of them referred basiliximab use for induction therapy in selected patients. Tailoring of immunosuppression was universally accepted, particularly in autoimmune hepatitis (AIH) (59%), hepatocellular carcinoma (54%) kidney dysfunction (77%) and primary biliary cirrhosis (33%). Weaning of corticosteroids at three, six and 12 months after LT was reported, respectively, by 41%, 36% and 23% of the centers, but policy for lifelong corticosteroid use in AIH-transplanted subjects was commonly observed (90%). Just four centers are currently performing protocol liver biopsies, while 18 of them are considering liver biopsy prior to steroid pulse therapy. HBIG and nucleos(t)ide analogs are used in most instances (73%) for HBV recurrence prevention, whereas CMV infection prophylaxis was shown to vary sharply across centers. Of note, all but two of them referred major changes in LT practice over the years due to economical restraints.

Conclusions

Compliance with standard of care recommendations for management of LT was reported by most centers. Heterogeneity in practices regarding HBV infection recurrence and CMV prophylaxis may reflect local financial restraints and point to the importance of developing ALEH guidelines to encourage LT activity in LATAM.

Introduction and Objectives

The PNPLA3 rs738409 C>G polymorphism has been associated with hepatocellular carcinoma (HCC) and liver cirrhosis regardless of the etiology, although the association was stronger with non-viral etiologies. However, the influence of PNPLA3 polymorphism on Hepatitis C Virus (HCV) and whether this polymorphism could be a risk factor for HCV-related HCC is not well defined. We aimed to evaluate the influence of the PNPLA3 rs738409 C>G polymorphism on the risk of HCC occurrence in HCV patients in Brazil.

Materials and Methods

This study included 90 patients with HCV-related cirrhosis and HCC who underwent liver transplantation or resection at a tertiary center in Brazil and 111 patients non-HCC with HCV-related cirrhosis, as the control group. The rs738409 polymorphism was detected in the DNA extracted from patients' blood samples using the TaqMan assay. All clinical data were collected using the Research Electronic Data Capture (REDCap) tool. The statistical analyses were performed using Jamovi software version 2.3.23.

Results

In the HCV+HCC group there was a higher proportion of male gender (79.1% vs. 45.9%, p<0.001), history of alcoholism (80.5% vs. 22.5%, p<0.001) and smoking (68.9% vs. 25.2%, p<0.001), however there was no statistical difference in age (p=0.519) and BMI (p=0.403) between both groups. The genotype frequencies of the rs738409 polymorphism in the HCV+HCC group was CC 41,2% CC and CG/GG 58,8% vs. controls CC 49,5% and CG/GG 50,5%. The presence of the G allele was not an independent factor associated with the risk of HCC occurrence (r=0,199, p=0.53).

Conclusions

Even in an admixed population such as the Brazilian, there was no association between the PNPLA3 rs738409 C>G polymorphism and the risk of developing HCV-related HCC, as previously shown in published studies in caucasian and oriental population.

Introduction and Objectives

Cirrhosis is a prevalent disease worldwide, with complications such as acute kidney injury (AKI) that increase the risk of fatal outcomes. A high BUN/creatinine ratio (IBC) has been associated with mortality in other diseases Therefore, evaluating this index in patients with cirrhosis could predict mortality. To determine whether a high BUN/creatinine ratio is associated with mortality in patients with cirrhosis and AKI.

Materials and Patients

Retrospective analysis was conducted on a cohort of cirrhotic patients with and without AKI, calculating the IBC and assessing its association with mortality.

Results

A total of 201 patients with cirrhosis were included, of whom 106 were male (52.73%), with a mean age of 55±10.4 years. The distribution of Child Pugh scores was as follows: A (25, 12.43%), B (70, 34.82%), and C (106, 52.73%); the mean MELD-Na score was 21.8±9.45. The cumulative mortality rate at 28 days was 37 (18.4%) and at 90 days was 39 (24.4%). The model was not significant at 28 days but was significant at 90 days with a X2 value of 48.18 (2) and p<0.001.

At 90 days, the model was significant with a x2 value of 49.7 (2) and p<0.001, with an OR (IBC) of 2.78 (1.08-7.11, 95% CI, p=0.33), and for AKI OR of 7.97 (2.2-28.8, 95% CI, p=0.02) (Figure 1). Considering either factor present, the model was significant at 28 days with a X2 of 27.75 (1) and p<0.001, with an OR of 7.2 (3-17.3, p<0.001), and at 90 days with a X2 of 35.59 (1) and p<0.001, with an OR of 6.67 (3.23-13.76, p<0.001).

Conclusions

The Cox proportional hazards model was used to compare factors associated with mortality separately for AKI (present vs. absent) and IBC (>20 mg/dl vs. <20 mg/dl) at 28 and 90 days, as well as if both factors were present. The model was considered significant if the p-value was less than 0.5. The study concluded that a higher IBC (>20 mg/dl) could predict mortality in patients with cirrhosis, as the odds ratios at 28 and 90 days were significant.

Introduction and Objectives

Hepatic encephalopathy (HE) is a common and serious complication of cirrhosis, associated with high morbidity and mortality. Ammonia and inflammation are the main triggers of HE. The use of L-ornithine-L-aspartate (LOLA) provides precursor substances for glutamine synthesis in perivenous cells, accelerating ammonia detoxification.

This study aims to evaluate the efficacy and safety of intravenous L-ornithine-L-aspartate (LOLA) in patients with grade III-IV hepatic encephalopathy (HE).

Materials and Patients

Retrospective and analytical study of patients with grade III-IV hepatic encephalopathy (HE).

All patients received intravenous LOLA 50 g for up to 48 hours, excluding those with renal failure. Descriptive statistics with measures of central tendency and dispersion were performed. Improvement was considered when HE regressed by at least one grade, and adverse events were evaluated.

Results

A total of 32 patients were included, with a mean age of 55 years ± 9.6. There were 13 females (40.6%) and 19 males (59.4%). Eight patients (25%) were classified as Child-Pugh B, while 24 patients (75%) were classified as Child-Pugh C. The mean MELD score was 19.03 ± 6.08, and the mean MELD NA score was 7.19 ± 7.19. The most common etiology was alcohol-related (43.8%), followed by MAFLD (29.1%) and viral (9.5%). All patients had grade III hepatic encephalopathy. The precipitating factors were sepsis (53%), hemorrhage (25%), constipation (12.5%), diuretics (6.3%), and electrolyte imbalance (3.1%). A total of 24 patients (75%) responded to the treatment, while 8 patients (25%) did not. Nineteen patients were found to have some degree of acute-on-chronic liver failure (ACLF). No adverse events were reported.

Conclusions

The use of intravenous LOLA for the treatment of grade III-IV hepatic encephalopathy iseffective and safe. These results support the use of LOLA as a therapeutic option in the management of hepatic encephalopathy in this patient population.

Introduction and Objectives

Liver transplantation is the optimal treatment in patients with irreversible liver damage. The principal complication of a transplant is ischemia-reperfusion injury (I/R), which induces primary graft rejection. Treatment with plant extracts prior to I/R has decreased the severity of this injury due to their potential anti-inflammatory and antioxidant activity. A plant that presents potential antioxidant activity is Flourensia cernua (Fc). The objective was to evaluate the hepatoprotective effect of Flourensia cernua against the damage induced by ischemia-reperfusion in Wistar rats.

Materials an Patients

42 mixed Wistar rats were sorted into 7 groups (n=6). Fc was administered (200 mg/kg/, p.o/5 days) followed by I/R clamping of the left portal triad producing 1hr of 70% ischemia and 2 or 24hrs of reperfusion. Biochemical and oxidative stress biomarkers, proinflammatory cytokine and gene expression were determined. Ethics Committee approval under HI17-00002 registry and PAICYT 152-CS-2022 financing. The research group declares no conflict of interest.

Results

The I/R groups with 2 (IR2hr) and 24 hour (IR24hr) reperfusion displayed significantly elevated ALT and AST concentrations vs. Sham (SH); only FcIR2hr significantly decreased these enzymes (Figure 1). The remaining biochemical parameters did not show any significant differences between the groups. IR2hr group induced a statistically significant alteration of oxidative stress biomarkers, Fc counteracted these effects, with a decrease of malondialdehyde(MDA) and an increase of reduced glutathione (GSH) and the superoxide dismutase(SOD) (Figure 2). The gene expression of NFκβ was increased in IR2hr group, the treatment with F. cernua counteracted this increase. TNF-α was significantly increased in the IR2hr group and decreased in the treatment group.

Conclusions

I/R is a widely studied injury model, capable of inducing pathological changes in several spheres, not unlike the observed results in the present study; the hydroalcoholic extract of Fc displayed anti-inflammatory and antioxidant activity at 200mg/kg, it was not toxic and proved to be hepatoprotective against I/R.

Introduction and Objectives

The hepatitis A and hepatitis E viruses are organisms that stand out for their high resistance to acid and alkaline media, as well as to freezing temperatures. Despite presenting an approximate mortality of 1% for both viruses, a seroprevalence of up to 81.3% has been reported in previous decades, so it is important to know the current epidemiological status of both diseases.

Materials and Patients

Cross-sectional, descriptive, prospective and observational study. Individuals over 18 years of age were recruited, who were studying or had the degree of gastroenterologists at the Hospital de Especialidades Centro Médico Nacional Siglo XXI, in a period of time between June 01 and June 30, 2023. Blood samples were collected for detection of immunoglobulin G against hepatitis A and hepatitis E viruses and a demographic questionnaire was conducted to each of the participants.

Results

23 individuals were recruited, 60.9% men (n=14) and 39.1% women (n=9), with a median age of 29 years, 13.0% corresponding to individuals from Mexico City (n= 3) and 86.9% from other states of the Mexican Republic (n=20). A seroprevalence of 17.3% (n=4) and 4.3% (n=1) was reported for hepatitis A virus and hepatitis E virus, respectively.

Conclusions

There is a lower seroprevalence for hepatitis A and hepatitis E viruses than reported, so it is vitally important to take preventive measures in populations at risk of infection, such as health personnel.