Can Liver Ultrasound Elastography Predict the Risk of Hepatocellular Carcinoma Recurrence After Radiofrequency Ablation? A Systematic Review and Meta-Analysis.

PURPOSE: The role of liver stiffness (LS) on ultrasound elastography in the prediction of hepatocellular carcinoma (HCC) recurrence after treatment with radiofrequency ablation (RFA) is still unclear. Our aim was to perform a systematic review and meta-analysis to assess whether LS can predict the recurrence of HCC after RFA. MATERIALS AND METHODS: Medline via PubMed, Embase, Scopus, and Cochrane Library databases, and abstracts of international conference proceedings were searched up to June 30, 2020. Cohort studies were included if they assessed the association between LS values measured by ultrasound elastography before RFA and HCC recurrence. RESULTS: 9 studies including 1373 patients with HCC treated by RFA, 643 of whom developed HCC recurrence, were identified. The mean value of LS before RFA was significantly higher in patients who developed HCC recurrence than in those who did not (weighted mean difference=11.98 kPa, 95%CI: 7.60-16.35, I2=63.8%). There was a significant positive association between LS value and HCC recurrence both at univariate (unadjusted HR=1.03, 95%CI: 1.00-1.07, I2=72.7%) and multivariate analysis (adjusted HR=1.03, 95%CI: 1.02-1.04, I2=0). Patients with LS value ≥13-14 kPa or >1.5 m/s have a higher risk of both HCC recurrence (unadjusted HR=2.18, 95%CI: 1.46-3.25, I2=49.7%; adjusted HR=2.41, 95%CI: 1.53-3.79, I2=0) and overall mortality (adjusted HR=4.38; 95%CI: 2.33-8.25, I2=0) in comparison with those with LS below these cutoffs. CONCLUSION: Liver ultrasound elastography appears to be a reliable tool to predict HCC recurrence and overall survival after RFA. This technique may be useful for the management of patients with HCC treated by RFA.

Proton pump inhibitors: Risks of long-term use.

Proton pump inhibitors are among the most commonly prescribed classes of drugs, and their use is increasing, in particular for long-term treatment, often being over-prescribed and used for inappropriate conditions. In recent years, considerable attention has been directed towards a wide range of adverse effects, and even when a potential underlying biological mechanism is plausible, the clinical evidence of the adverse effect is often weak. Several long-term side effects have been investigated ranging from interaction with other drugs, increased risk of infection, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia. The most recent literature regarding these adverse effects and their association with long-term proton pump inhibitor treatment is reviewed, and the mechanisms through which these possible complications might develop are discussed.

Relationship between indocyanine green retention test, decompensation and survival in patients with Child-Pugh A cirrhosis and portal hypertension.

BACKGROUND & AIMS: Indocyanine green retention test (ICG-r15) is a non-invasive marker of functional hepatic reserve. Among patients with compensated cirrhosis, ICG-r15 correlates to the degree of portal hypertension (PH); however, its prognostic relationship with the occurrence of decompensation events still requires clarification. METHODS: ICG-r15 was prospectively measured in 154 patients with compensated cirrhosis. Patients with hepatocellular carcinoma (HCC), Child-Pugh B-C, MELD>15, bilirubin > 2 mg/dl, INR > 1.5 or portal vein thrombosis were excluded. All patients underwent laboratory tests, upper endoscopy and hepatic venous pressure gradient (HVPG). Decompensation, development of HCC, liver transplant and death were recorded and analysed through competing-risk analysis. RESULTS: The study group was composed of 134 patients who were followed for a median of 39 months. During follow-up, 46 patients (34.3%) developed liver decompensation. Hepatocellular carcinoma occurred in 18 patients and two patients died from non-liver-related causes. The 1-, 2- and 3-year cumulative incidences of decompensation were 9.7%, 28.4% and 33.4% respectively. Patients with ICG-r15 < 10% did not experience any decompensation events during follow-up, while the 3-year cumulative incidence of decompensation of patients with ICG-r15 between 10% and 22.9% was 29.2% and that of patients with ICG-r15 ≥ 23% was 70.0% (P < 0.001). ICG-r15 gave the lowest pseudo-log-likelihood value, in comparison to oesophageal varices present, MELD, low platelet count and HVPG. CONCLUSIONS: ICG-r15 appears to be strictly related to liver decompensation, longitudinally confirming the preliminary findings of its correlation with PH among patients with compensated cirrhosis, and can be used for patient prognostication.

Indocyanine green retention test as a noninvasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis.

UNLABELLED: Noninvasive markers would be useful for the assessment of portal hypertension (PH) and esophageal varices (EV) in patients with cirrhosis. The aim of our study was to evaluate the performance of the indocyanine green (ICG) retention test as a noninvasive marker of PH and EV, measured against the gold standards (hepatic venous pressure gradient [HVPG] measurement and upper endoscopy). We prospectively enrolled patients with compensated cirrhosis referral to our unit. All patients underwent laboratory tests, abdominal ultrasound, upper gastrointestinal endoscopy, HVPG measurement, and the ICG 15-minute retention (ICG-r15) test. We evaluated the sensitivity and specificity of the ICG retention test and other noninvasive tools for the diagnosis of PH and EV. Ninety-six consecutive Child-Pugh A patients (67 male and 29 female; 60.3 ± 11.8 years of age) were enrolled. Seventy-four patients had clinically significant portal hypertension (CSPH), of whom 59 had severe portal hypertension (SPH). ICG-r15 and Lok index were independently related to the presence of both CSPH and SPH, whereas ICG-r15 and INR were related to EV. ICG-r15 values (<6.7% and <6.9%, respectively) were able to rule out the presence of CSPH and SPH (LR(-) 0.15 and 0.14); ICG-r15 <10% provided a 97.8% sensitivity (LR(-) 0.042) for the exclusion of EV and a 100% sensitivity (LR(-) 0.0) for large EV. CONCLUSION: The ICG-r15 test is an effective tool for assessment of PH in patients with compensated cirrhosis. Although this would not replace endoscopy, the ICG-r15 appears able to identify patients with advanced liver disease in which endoscopy is mandatory as well as rule out the presence of EV in patients with compensated cirrhosis.

Acute Fitz-Hugh-Curtis syndrome in a man due to gonococcal infection.

BACKGROUND: Fitz-Hugh-Curtis syndrome is a rare extra-pelvic complication of genital infection involving the perihepatic capsule. Most cases have been described in women in association with pelvic inflammatory disease; in rare cases it has been reported in men. Because the main symptom is acute abdominal pain, and laboratory and imaging findings are frequently nonspecific, the differential diagnosis, considering other gastrointestinal or renal diseases, can be difficult in the early stage of the syndrome, leading to frequent misdiagnosis and mismanagement. CASE REPORT: We report a case of Fitz-Hugh-Curtis syndrome in a 26-year-old man who first presented to the emergency department with acute abdominal pain, vomiting, and fever. Diagnosis was possible on the basis of clinical signs of orchiepididymitis, abnormal ultrasound findings, and specialist consultation with the Sexually Transmitted Infection Clinic. An acute gonoccocal infection was revealed, which was complicated by a collection of free perihepatic fluid and a subcapsular hypoechoic focal lesion. Prompt antibiotic therapy was established, with complete resolution of the symptoms within a few days. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Awareness of the clinical presentation, imaging, and laboratory findings during the acute phase of Fitz-Hugh-Curtis syndrome could help emergency physicians to make an early diagnosis and to correctly manage such patients. Improved diagnostic skills could prevent chronic complications that are especially a risk in the case of delayed or minor genitourinary symptoms.

Semisynthetic bile acid FXR and TGR5 agonists: physicochemical properties, pharmacokinetics, and metabolism in the rat.

We report on the relationship between the structure-pharmacokinetics, metabolism, and therapeutic activity of semisynthetic bile acid analogs, including 6α-ethyl-3α,7α-dihydroxy-5ß-cholan-24-oic acid (a selective farnesoid X receptor [FXR] receptor agonist), 6α-ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5ß-cholan-24-oic acid (a specific Takeda G protein-coupled receptor 5 [TGR5] receptor agonist), and 6α-ethyl-3α,7α-dihydroxy-24-nor-5ß-cholan-23-sulfate (a dual FXR/TGR5 agonist). We measured the main physicochemical properties of these molecules, including ionization constants, water solubility, lipophilicity, detergency, and protein binding. Biliary secretion and metabolism and plasma and hepatic concentrations were evaluated by high-pressure liquid chromatography-electrospray-mass spectrometry/mass spectrometry in bile fistula rat and compared with natural analogs chenodeoxycholic, cholic acid, and taurochenodexycholic acid and intestinal bacteria metabolism was evaluated in terms of 7α-dehydroxylase substrate-specificity in anaerobic human stool culture. The semisynthetic derivatives detergency, measured in terms of their critical micellar concentration, was quite similar to the natural analogs. They were slightly more lipophilic than the corresponding natural analogs, evaluated by their 1-octanol water partition coefficient (log P), because of the ethyl group in 6 position, which makes these molecules very stable toward bacterial 7-dehydroxylation. The hepatic metabolism and biliary secretion were different: 6α-ethyl-3α,7α-dihydroxy-5ß-cholan-24-oic acid, as chenodeoxycholic acid, was efficiently conjugated with taurine in the liver and, only in this form, promptly and efficiently secreted in bile. 6α-Ethyl-23(S)-methyl-3α,7α,12α-trihydroxy-5ß-cholan-24-oic acid was poorly conjugated with taurine because of the steric hindrance of the methyl at C23(S) position metabolized to the C23(R) isomer and partly conjugated with taurine. Conversely, 6α-ethyl-3α,7α-dihydroxy-24-nor-5ß-cholan-23-sulfate was secreted in bile unmodified and as 3-glucuronide. Therefore, minor structural modifications profoundly influence the metabolism and biodistribution in the target organs where these analogs exert therapeutic effects by interacting with FXR and/or TGR5 receptors.

The Diagnosis and Treatment of Acute Cholecystitis: A Comprehensive Narrative Review for a Practical Approach.

Acute cholecystitis (AC), generally associated with the presence of gallstones, is a relatively frequent disease that can lead to serious complications. For these reasons, AC warrants prompt clinical diagnosis and management. There is general agreement in terms of considering early laparoscopic cholecystectomy (ELC) to be the best treatment for AC. The optimal timeframe to perform ELC is within 72 h from diagnosis, with a possible extension of up to 7-10 days from symptom onset. In the first hours or days after hospital admission, before an ELC procedure, the patient's medical management comprises fasting, intravenous fluid infusion, antimicrobial therapy, and possible administration of analgesics. Additionally, concomitant conditions such as choledocholithiasis, cholangitis, biliary pancreatitis, or systemic complications must be recognized and adequately treated. The importance of ELC is related to the frequent recurrence of symptoms and complications of gallstone disease in the interval period between the onset of AC and surgical intervention. In patients who are not eligible for ELC, it is suggested to delay surgery at least 6 weeks after the clinical presentation. Critically ill patients, who are unfit for surgery, may require rescue treatments, such as percutaneous or endoscopic gallbladder drainage (GBD). A particular treatment approach should be applied to special populations such as pregnant women, cirrhotic, and elderly patients. In this review, we provide a practical diagnostic and therapeutic approach to AC, even in specific clinical situations, based on evidence from the literature.

A patient with pancreas divisum, recurrent acute pancreatitis, and homozygosity for the cystic fibrosis transmembrane regulator-associated protein 5T allele.

Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) have been reported to increase the risk of recurrent acute pancreatitis in patients with pancreas divisum. We assessed the CFTR gene in a young male patient with pancreas divisum and recurrent acute pancreatitis. Magnetic resonance cholangiopancreatography and computed tomography revealed that the patient had pancreas divisum, with an enlarged and tortuous pancreatic duct; he also had positive results from the cystic fibrosis sweat test. Genetic analysis did not identify any common CFTR mutations, but did show that he was homozygous for the 5T allele in intron 8 IVS8 5T-12TG (which affects splicing at intron 8). Endoscopic sphincterotomy and stenting of papilla minor was performed. The IVS8 5T-12TG variant has been associated with abnormal organ development, therefore it is possible that CFTR has an important role in the development of the pancreatic duct. We propose this patient has recurrent acute pancreatitis resulting from a developmental defect associated with a suboptimal CFTR function.

Utility of Doppler-Ultrasound and Liver Elastography in the Evaluation of Patients with Suspected Pregnancy-Related Liver Disease.

Grayscale abdomen ultrasound (US) is routinely performed in pregnant women with suspected pregnancy-related liver dysfunction, but its diagnostic yield is very low. We aimed to investigate the association between Doppler-US findings, liver stiffness measurement (LSM) and different causes of pregnancy-related liver dysfunction. This is a prospective cohort study of pregnant women referred to our tertiary center for any suspected gastrointestinal disease between 2017 and 2019 and undergoing Doppler-US and liver elastography. Patients with previous liver disease were excluded from the analysis. For group comparisons of categorical and continuous variables, the chi-square test or Mann-Whitney test, and the McNemar test were used, as appropriate. A total of 112 patients were included in the final analysis, of whom 41 (36.6%) presented with suspected liver disease: 23 intrahepatic cholestasis of pregnancy (ICP), six with gestational hypertensive disorders and 12 cases with undetermined causes of elevated liver enzymes. Values of LSM were higher and significantly associated with a diagnosis of gestational hypertensive disorder (AUROC = 0.815). No significant differences at Doppler-US or LSM were found between ICP patients and controls. Patients with undetermined causes of hypertransaminasemia showed higher hepatic and splenic resistive indexes than controls, suggesting splanchnic congestion. The evaluation of Doppler-US and liver elastography is clinically useful in patients with suspected liver dysfunction during pregnancy. Liver stiffness represents a promising non-invasive tool for the assessment of patients with gestational hypertensive disorders.

Dual-color bioluminescent assay using infected HepG2 cells sheds new light on Chlamydia pneumoniae and human cytomegalovirus effects on human cholesterol 7α-hydroxylase (CYP7A1) transcription.

Chlamydia pneumoniae and human cytomegalovirus (HCMV) are intracellular pathogens able to infect hepatocytes, causing an increase in serum triglycerides and cholesterol levels due to the production of inflammatory cytokines. We investigated whether these pathogens could interfere with cholesterol metabolism by affecting activity of hepatic cholesterol 7α-hydroxylase (CYP7A1) promoter. CYP7A1 is the rate-limiting enzyme responsible for conversion of cholesterol to bile acids, which represents the main route of cholesterol catabolism. A straightforward dual-reporter bioluminescent assay was developed to simultaneously monitor CYP7A1 transcriptional regulation and cell viability in infected human hepatoblastoma HepG2 cells. C. pneumoniae and HCMV infection significantly decreased CYP7A1 promoter activity in a dose-dependent manner, with maximal inhibitions of 33±10% and 32±4%, respectively, at a multiplicity of infection of 1. To support in vitro experiments, serum cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and glucose levels were also measured in Balb/c mice infected with C. pneumoniae. Serum cholesterol and triglycerides also increased in infected mice compared with controls. Although further investigation is required, this work presents the first experimental evidence that C. pneumoniae and HCMV inhibit CYP7A1 gene transcription in the cultured human hepatoblastoma cell line.

Reduced biliary sterol output with no change in total faecal excretion in mice expressing a human apolipoprotein A-I variant.

BACKGROUND/AIMS: Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). METHODS: ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. RESULTS: The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. CONCLUSIONS: In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines.

High dose lamivudine in HBV-related cirrhotic patients with unsatisfactory response after adefovir add-on.

BACKGROUND: Before tenofovir approval for chronic hepatitis B therapy, the clinical management of patients with suboptimal response or virological breakthrough during combination treatment with lamivudine and adefovir dipivoxil was a difficult clinical challenge. AIMS: In order to improve virologic response and reduce the risk of decompensation, we evaluate the efficacy of a high dose of lamivudine on chronic HBV patients who have previously presented an unsatisfactory response during treatment with lamivudine 100mg/day and adefovir 10mg/day. METHODS: Six patients with HBV-related liver cirrhosis were prospectively enrolled. All were HBeAg-negative and presented a suboptimal response or virological breakthrough after "adefovir add-on" because of development of clinical breakthrough during Lamivudine treatment. Lamivudine dose was increased to 200 or 300 mg, depending on viral load. After 12 months of follow-up, virological and biochemical response were evaluated. RESULTS: After 12 months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant decrease of serum HBV DNA (mean reduction 2,62 ± 1,15 Log10 UI/ml, P = 0.03) and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable within 6 months. No patient developed liver decompensation and no significant changes occurred in serum creatinine, serum and urinary electrolytes. No adverse events were registered. CONCLUSIONS: In our experience, rescue strategy with high-dose lamivudine inhibited viral replication leading to undetectability of serum HBVDNA. This rescue treatment presented a good safety profile, without adverse events during the study period. Customized increase of nucleos(t)ide analogues dose in difficult-to-treat patients may be a proficient approach in challenging clinical setting.

First Isolation of Yarrowia lipolytica in a Granulomatous Pneumonia of a Spectacled Caiman, Caiman crocodilus Linnaeus, 1758.

Contrary to humans, candidiasis is a rare infection in animals. However, in reptiles, candidiasis can cause gastrointestinal, cutaneous, or rarely systemic infections in stressed animals. The infections due to Yarrowia lipolytica have been increasingly described in human medicine, and hundreds of cases are reported, comprised of granulomatous lung lesions. Herein, granulomatous pneumonia of a spectacled caiman, Caiman crocodilus, was described, and the presence of Y. lipolytica in the lesion was confirmed through histopathology, microbiologic cultures, and molecular methods. The cause of death of the spectacled caiman was ascribed to bacterial shock septicemia consequentially to a traumatic lesion. However, in the right lung, several nodules containing white exudate were evidenced. At mycological and molecular analyses, Y. lipolytica was evidenced, and the histological finding confirmed the presence of a Candida infection in the lung granulomatous lesions. The comparison of ITS sequences with 11 Yarrowia spp. isolates, recently described in green sea turtles, and with a human strain was conducted, and the whole genome of a strain isolated in the spectacled caiman was sequenced. Even though Y. lipolytica is considered a non-pathogenic yeast and has been rarely described in animals, it seems to cause granulomatous lesions in reptiles as in humans.

Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis.

INTRODUCTION: Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis. METHODS: Guidelines were developed by the Italian Societies of Gastroenterology. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists and a paediatrician with expertise in this field. RESULTS: These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and management of dermatitis herpetiformis. CONCLUSIONS: These guidelines may support clinicians to improve the diagnosis and management of patients with coeliac disease.

Approaches to the Diagnosis of Portal Hypertension: Non-Invasive or Invasive Tests?

Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD) and is defined by values of hepatic venous pressure gradient measurement (HVPG) >5 mmHg. Values of HVPG ≥10 mmHg determine the presence of clinically significant portal hypertension (CSPH), the main predictor of the risk of variceal bleeding, hepatic decompensation, and mortality. However, its measurement is invasive and requires high expertise, so its routine use outside third level centers or clinical trials is limited. In the last decades, several non-invasive tests (NITs) have been developed and validated for the diagnosis of portal hypertension. Among these, liver (LSM) and spleen stiffness measurement (SSM) are the most promising tools available, as they have been proven accurate to predict CSPH, high-risk esophageal varices, decompensation, and mortality in patients with ACLD. In the last Baveno VI Consensus proceedings, LSM evaluation was recommended for the first time for diagnosis of CSPH (LSM >20-25 kPa) and the screening of patients with a low probability of having high-risk varices (LSM <20 kPa and platelet count >150.000/mm3). In this review, we aimed to summarize the growing evidence supporting the use of non-invasive tests for the evaluation of portal hypertension in patients with chronic liver disease.

Prognostic Value of the Albumin-Bilirubin Grade for the Prediction of Post-Hepatectomy Liver Failure: A Systematic Review and Meta-Analysis.

(1) Introduction: Liver resection (LR) for hepatocellular carcinoma (HCC) is often burdened by life-threatening complications, such as post-hepatectomy liver failure (PHLF). The albumin-bilirubin (ALBI) score can accurately evaluate liver function and the long-term prognosis of HCC patients, including PHLF. We aimed to evaluate the diagnostic value of the ALBI grade in predicting PHLF in HCC patients undergoing LR. (2) Methods: MEDLINE, Embase, and Scopus were searched through January 17th, 2021. Studies reporting the ALBI grade and PHLF occurrence in HCC patients undergoing LR were included. The Odds Ratio (OR) prevalence with 95% confidence intervals (CI) was pooled, and the heterogeneity was expressed as I2. The quality of the studies was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). (3) Results: Seven studies met the inclusion criteria and were included in the analysis. A total of 5377 patients who underwent LR for HCC were considered, of whom 718 (13.4%) developed PHLF. Patients with ALBI grades 2 and 3 before LR showed increased rates of PHLF compared to ALBI grade 1 patients. The pooled OR was 2.572 (95% CI, 1.825 to 3.626, p < 0.001), with substantial heterogeneity between the studies (I2 = 69.6%) and no publication bias (Begg's p = 0.764 and Egger's p = 0.851 tests). All studies were at a 'low risk' or 'unclear risk' of bias. Univariate meta-regression analysis showed that heterogeneity was not dependent on the country of study, the age and sex of the participants, the definition of PHLF used, the rate of patients in Child-Pugh class A or undergoing major hepatectomy. (4) Conclusions: In this meta-analysis of published studies, individuals with ALBI grades of 2 and 3 showed increased rates of PHLF compared to ALBI grade 1 patients.

Lamivudine treatment for severe acute HBV hepatitis.

Treatment for acute hepatitis B is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of OLT. We report our experience on treatment with high dose lamivudine, in patients with severe acute HBV infection. The diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage. The decision to treat was based on the prolongation of INR together with increasing values of bilirubin and ALT. Four patients received Lamivudine 200 mg/daily until clearance of serum HBV-DNA and then 100 mg/daily until clearance of HBsAg and appearance of anti-HBs antibodies. One patient received 100 mg/daily because of chronic renal impairment. The median period of hospitalization was 13 days, and none of the patients had complications, related either to underlying disease or to therapy. The complete normalization of serum transaminases and bilirubin occurred on average after 5.5 weeks and 3 weeks respectively. All patients cleared serum HBV-DNA within three months, lost HBeAg and HBsAg and seroconverted to anti-HBe; four patients developed anti-HBs at a protective titre. Early antiviral treatment attenuates the clinical and biochemical impairment leading to fast healing and promoting complete recovery.

Noninvasive Assessment of Portal Hypertension in Advanced Chronic Liver Disease: An Update.

The assessment of portal hypertension is a relevant step in the evaluation of newly diagnosed advanced chronic liver disease (ACLD). The current gold standard includes the invasive evaluation of hepatic venous pressure gradient (HVPG) and endoscopy. However, noninvasive or minimally invasive techniques to assess portal hypertension have been proposed and well established. In the present manuscript, we review clinical studies on the use of noninvasive or minimally invasive techniques to assess portal hypertension in ACLD patients.