Severe Chronic Liver Disease Research Articles

Characterization of a Threonine-Rich Cluster in Hepatitis C Virus Nonstructural Protein 5A and Its Contribution to Hyperphosphorylation.

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a phosphoprotein with key functions in regulating viral RNA replication and assembly. Two phosphoisoforms are discriminated by their different apparent molecular weights: a basally phosphorylated (p56) and a hyperphosphorylated (p58) variant. The precise mechanisms governing p58 synthesis and specific functions of the isoforms are poorly understood. Our study aimed at a deeper understanding of determinants involved in p58 synthesis. We analyzed two variants of p56 and p58 of isolate JFH-1 separately by mass spectrometry using an expression model and thereby identified a threonine-rich phosphopeptide exclusively found in the hyperphosphorylated variant. Individual exchange of possible phosphoacceptor sites to phosphoablatant or -mimetic residues had little impact on HCV replication or assembly in cell culture. A phosphospecific antibody recognizing pT242 revealed that this position was indeed phosphorylated only in p58 and depended on casein kinase Iα. Importantly, phosphoablative mutations at positions T244 and S247 abrogated pT242 detection without substantial effects on global p58 levels, whereas mutations in the preceding serine-rich cluster dramatically reduced total p58 levels but had minor impact on pT242 levels, suggesting the existence of distinct subspecies of hyperphosphorylated NS5A. Mass spectrometry analyses of different genotypes showed variable phosphorylation patterns across NS5A and suggested that the threonine-rich region is also phosphorylated at T242 in gt4a and at S249 in gt1a, gt1b, and gt4a. Our data therefore indicate that p58 is not a single homogenously phosphorylated protein species but rather a population of various phosphoisoforms, with high variability between genotypes.IMPORTANCE Hepatitis C virus infections affect 71 million people worldwide and cause severe chronic liver disease. Recently, efficient antiviral therapies have been established, with inhibitors of nonstructural protein NS5A as a cornerstone. NS5A is a central regulator of HCV replication and assembly but is still enigmatic in its molecular functions. It exists in two phosphoisoforms, p56 and p58. We identified a phosphopeptide exclusively found in p58 and analyzed the determinants involved in phosphorylation of this region. We found evidence for very different phosphorylation patterns resulting in p58. These results challenge the concept of p58 being a homogenous species of NS5A molecules phosphorylated at the same positions and argues for at least two independently phosphorylated variants showing the same electrophoretic mobility, likely serving different functions.

Transjugular intrahepatic portosystemic shunt as a bridge to liver transplant: Current state and future directions.

Liver transplantation is one of the mainstays of treatment for liver failure due to severe chronic liver disease. Bridging therapies, such as placement of a transjugular intrahepatic portosystemic shunt (TIPS), are frequently employed to control complications of portal hypertension such as ascites, hydrothorax, and variceal bleeding, and thereby reduce morbidity in patients awaiting transplant. There is no significant difference seen in either graft survival or patient survival between those receiving TIPS pre-transplant and those who do not, although those receiving TIPS placement on average have a longer waiting time on the transplant waitlist. Locoregional therapies, such as thermal ablation or chemoembolization, can be efficacious in patients with HCC and pre-existing TIPS; however there is a risk for increased adverse events in patients receiving these therapies who have TIPS compared to those who do not. In summary, TIPS is a safe, effective treatment that can be used to ameliorate the complications that are sequelae of portal hypertension. While it does not appear to improve survival post-transplant, TIPS placement pre-transplant may increase survival time to transplant, thus improving overall survival as well as quality of life.

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells.

Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear. Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non-PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High-dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to Escherichia coli and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSC-patients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC.

Laparoscopic liver resection for the patients with hepatocellular carcinoma and chronic liver disease.

Liver resection (LR), liver transplantation (LT), transarterial chemoembolization, and local ablation therapy are the treatment options for hepatocellular carcinoma (HCC). Although LR, LT and local ablation therapy (only for small tumor) provide the best hope for cure, most patients with HCC have also chronic liver disease (CLD) backgrounds, including HCV-liver cirrhosis. Therefore, they are at high risk for development of postoperative complications-sometimes fatal-and metachronous multicentric recurrent tumors occurring from the preneoplastic CLD background. Appropriate treatment is selected for HCC patients, on the combined evaluations of tumor condition and liver function. However, not small number of patients cannot undergo any treatment option due to poor liver function and/or complicated tumor condition. After repeated treatments, it can happen more often. It is thought that the features of laparoscopic LR could lead to the expansion of the LR indication to those patients, in the settings of severe CLD, repeat LR and bridging to LT. In our experience, Child-Pugh (CP) score is one of the promising candidates as a selection indicator which correlates well to our indication criteria of surface small laparoscopic LR to severe CLD patients, patient's performance status, and prognosis. Portal hypertension should be also counted in the selection criteria.

Anaemia in patients with chronic liver disease and its association with morbidity and mortality following liver transplantation

Pre-operative anaemia and the need for intra-operative transfusion have been associated with increased morbidity and mortality following cardiac and major non-cardiac surgery. Anaemia is highly prevalent in patients with severe chronic liver disease. Whether this correlates with an altered morbidity and mortality following liver transplant has not been established. MethodsProspectively collected data was analysed for the period 1998–2012. Donor and recipient characteristics, blood profiles and complications were recorded. Graft and patient survival was calculated. All patients were followed up for 1 year or until death. Pre-operative haemoglobin levels were correlated with patient demographics and outcome using a binary logistic regression analysis. ResultsPre-operative anaemia, according to WHO criteria, occurred in 73% of patients. Anaemia was more common with advanced liver disease (higher MELD score). As MELD score increased, Haemoglobin levels dropped. Anaemic patients were more commonly transfused (p < 0.001), spent longer ventilated (7 day vs 5 days, p = 0.005) and required longer ITU stays (8 days vs 6 days, p = 0.015). Pre-operative anaemia did not correlate with patient morbidity or mortality. ConclusionsReduced haemoglobin levels reflect the severity of chronic liver disease but are not an independent risk factor for a poor outcome following liver transplantation.

Elevated serum heat shock protein 70 and liver stiffness reflect hepatic dysfunction and severity in postoperative biliary atresia.

Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients. One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography. BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P<0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1±2.1 vs. 27.9±2.5ng/mL, P<0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r=0.491, P<0.001), alanine aminotransferase (r=0.448, P<0.001), total bilirubin (r=0.303, P=0.002), alkaline phosphatase (r=0.414, P<0.001), and liver stiffness values (r=0.455, P<0.001). There was a negative correlation between serum HSP70 and serum albumin (r=-0.434, P=0.001). Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

Thromboelastometry: Relation to the severity of liver cirrhosis in patients considered for liver transplantation.

The severity of liver disease is assessed by scoring systems, which include the conventional coagulation test prothrombin time-the international normalized ratio (PT-INR). However, PT-INR is not predictive of bleeding in liver disease and thromboelastometry (ROTEM) has been suggested to give a better overview of the coagulation system in these patients. It has now been suggested that coagulation as reflected by tromboelastomety may also be used for prognostic purposes. The objective of our study was to investigate whether thrombelastometry may discriminate the degree of liver insufficiency according to the scoring systems Child Pugh and Model for End-stage Liver Disease (MELD).Forty patients with chronic liver disease of different etiologies and stages were included in this observational cross-sectional study. The severity of liver disease was evaluated using the Child-Pugh score and the MELD score, and blood samples for biochemistry, conventional coagulation tests, and ROTEM were collected at the time of the final assessment for liver transplantation. Statistical comparisons for the studied parameters with scores of severity were made using Spearman correlation test and receiver-operating characteristic (ROC) curves.Spearman correlation coefficients indicated that the thromboelastometric parameters did not correlate with Child-Pugh or MELD scores. The ROC curves of the thromboelastometric parameters could not differentiate advanced stages from early stages of liver cirrhosis.Standard ROTEM cannot discriminate the stage of chronic liver disease in patients with severe chronic liver disease.

Neurological disorders in liver transplant candidates: Pathophysiology and clinical assessment.

Compromised liver function, as a consequence of acute liver insufficiency or severe chronic liver disease may be associated with various neurological syndromes, which involve both central and peripheral nervous system. Acute and severe hyperammoniemia inducing cellular metabolic alterations, prolonged state of "neuroinflammation", activation of brain microglia, accumulation of manganese and ammonia, and systemic inflammation are the main causative factors of brain damage in liver failure. The most widely recognized neurological complications of serious hepatocellular failure include hepatic encephalopathy, diffuse cerebral edema, Wilson disease, hepatic myelopathy, acquired hepatocerebral degeneration, cirrhosis-related Parkinsonism and osmotic demyelination syndrome. Neurological disorders affecting liver transplant candidates while in the waiting list may not only significantly influence preoperative morbidity and even mortality, but also represent important predictive factors for post-transplant neurological manifestations. Careful pre-transplant neurological evaluation is essential to define severity and distribution of the neurological impairment, to identify the abnormalities still responsive to current treatment, and to potentially predict the inherent post-operative prognosis. The preferred specific indices of neurological pre-transplant assessment may vary among centers, however, even with the aid of the current biochemical, neurophysiological, neuropsychological and neuroimaging diagnostic tools, the correct diagnosis and differential diagnosis of various syndromes may be difficult. In this article the relevant pathophysiological and clinical aspects of the most frequent brain and peripheral nervous system diseases affecting liver transplant candidates with acute or advanced chronic liver failure are briefly reported. The practical diagnostic findings useful for the preoperative assessment and treatment, as well as the expected neurological evolution after liver transplantation are also evaluated.

Liver Involvement in Patients With PiZZ-Emphysema, Candidates for Lung Transplantation.

Information about the prevalence and nature of liver disorders in adults with alpha1-antitrypsin deficiency is scarce. At our center, systematic liver biopsy screening is part of the evaluation before lung transplantation (LT) in the emphysema patients with the PiZZ phenotype. Our aim was to report our experience with this prospective screening. Clinical, liver function, and imaging parameters as well as liver histology data were analyzed for 23 consecutive adult patients with PiZZ severe emphysema referred to our center for consideration of LT from 2006 to 2014. Overall 20 (87%) featured chronic liver disease characterized by a chronic inflammation and/or a significant portal fibrosis on histology. Two of the 23 patients (8.7%) had septal fibrosis according to the Metavir and Ishak scores and met our definition of severe chronic liver disease. They were both clinically asymptomatic with normal liver function tests. On abdominal ultrasonography, the liver appeared normal in one patient and with abnormal contours in the other. Our data indicate that in adults with PiZZ-related emphysema being evaluated for LT, most patients had some histologic involvement. The prevalence of severe liver dysfunction is <10%.

Coagulation in acutely ill patients with severe chronic liver disease: Insights from thromboelastography

Background and aimsThere is controversy about the true coagulation state of acutely ill patients with chronic liver disease (CLD) due to simultaneous pro- and anticoagulant factor deficits and limitations of conventional coagulation tests (CCTs). Thromboelastography (TEG) may provide more physiologically relevant insights. MethodsIn acutely ill patients with severe (Child-Pugh C) CLD, we conducted a prospective observational study of daily coagulation assessment with both CCTs and TEG. ResultsWe studied 34 patients with CLD on a total of 109 occasions (median of 3 samples per patient), comparing findings with 157 healthy controls. Conventional coagulation tests and TEG both demonstrated clear hypocoagulability. Thromboelastography-confirmed delayed clot formation was demonstrated by longer reaction time (1.1 minutes vs 0.6 minutes on rapid TEG; P<.01), longer kinetic time (2.9 minutes vs 1.3; P<.01), more acute α angle (65° vs 72.2°; P<.01), and longer activated clotting time (157 seconds vs 105 seconds; P<.01). Patients with CLD demonstrated weaker thrombus strength (maximum amplitude, 43.3 mm vs 61.8 mm; P<.01) and reduced clot lysis (0% vs 1% on rapid TEG; P<.01). ConclusionsIn acutely ill patients with CLD, TEG demonstrates delayed clot formation and weaker thrombus strength despite decreased clot lysis. This challenges the notion that such patients experience a balanced coagulation state, highlighting the complexity of their coagulopathies.

Hepatorenal Syndrome: Diagnosis and Treatment - newsreel.

Hepatorenal syndrome (HRS) is defined as renal failure that occurs in the presence of severe acute or chronic liver disease in the absence of underlying renal pathology. Due to the functional nature of the disease and the absence of specific diagnostic markers, HRS diagnosis is determined based on positive criteria associated with excluding other causes of renal failure in patients with liver cirrhosis and ascites. Differentiation from other types of acute or chronic renal disease is extremely difficult and therapeutic options are limited, prophylactic behavior is most appropriate in patients with severe hepatic disease and risk factors for the installation of hepatorenal syndrome. Highlighting all precipitating factors of acute renal insufficiency and therapeutic modalities in order to minimize adverse events is an important step in improving the follow-up of the patients with liver cirrhosis. The prognosis is reserved especially for type 1 HRS. Liver transplantation is the best option for patients without contraindications. The therapies introduced in recent years, such as vasoconstrictor drugs or transjugular intrahepatic portosystemic shunt are effective methods in the renal function improvement.

The role of vascular endothelial growth factor −634 G/C and its soluble receptor on chronic liver disease and hepatocellular carcinoma

Background and study aimsThe single nucleotide polymorphism (SNP) of the vascular endothelial growth factor (VEGF) gene −634 G/C (rs2010963) influences the progression of hepatocellular carcinoma (HCC). There have been no studies on the role of VEGF SNP −634 G/C in chronic liver disease (CLD). The aim of the present study was to analyse the correlation between VEGF SNP −634 and the clinical severity of CLD and HCC. Patients and methodsA cross sectional study was conducted on 182 subjects (46 HCC, 39 liver cirrhotic/LC, 38 chronic hepatitis/CH; and 57 healthy subjects). The study was conducted from 2010 to 2014 at the Dr. Sardjito Hospital Yogyakarta, Indonesia. All subjects submitted blood serum for DNA sequencing examination using primer. The clinical data of CLD and HCC were assessed, and sVEGFR-2 was examined in 149 subjects. All data were analysed using STATA programme 11.0. ResultsSignificant differences were observed in genotypic frequency (GG/GC/CC) between HCC, LC, CH and healthy subjects (p=0.004), but though no significant differences were observed between the G>G and C>G genotypic frequencies (p=0.337). The frequency of genotype GG was significantly higher than genotype GC or CC in HCC and was associated with declining of clinical conditions (p<0.05). No significant difference in the distribution genotypes was observed with respect to the level of sVEGFR-2 in the serum. However, we observed a significant correlation between sVEGFR-2 and clinical characteristics in LC and CH (p<0.05). ConclusionGenotype GG of the VEGF SNP −634 is the dominant genotype in severe CLD and HCC. sVEGFR-2 correlates with the disease severity but is not directly associated with the SNP −634 genotype.

Pulmonary complications of hepatic diseases.

Severe chronic liver disease (CLD) may result from portal hypertension, hepatocellular failure or the combination of both. Some of these patients may develop pulmonary complications independent from any pulmonary pathology that they may have. Among them the hepatopulmonary syndrome (HPS), portopulmonary hypertension (PPH) and hepatic hydrothorax (HH) are described in detail in this literature review. HPS is encountered in approximately 15% to 30% of the patients and its presence is associated with increase in mortality and also requires liver transplantation in many cases. PPH has been reported among 4%-8% of the patient with CLD who have undergone liver transplantation. The HH is another entity, which has the prevalence rate of 5% to 6% and is associated in the absence of cardiopulmonary disease. These clinical syndromes occur in similar pathophysiologic environments. Most treatment modalities work as temporizing measures. The ultimate treatment of choice is liver transplant. This clinical review provides basic concepts; pathophysiology and clinical presentation that will allow the clinician to better understand these potentially life-threatening complications. This article will review up-to-date information on the pathophysiology, clinical features and the treatment of the pulmonary complications among liver disease patients.

Can public health registry data improve Emergency Medical Dispatch?

Emergency Medical Dispatchers make decisions based on limited information. We aimed to investigate if adding demographic and hospitalization history information to the dispatch process improved precision. This 30-day follow-up study evaluated time-critical emergencies in contact with the emergency phone number 112 in Denmark during 18 months. 'Time-critical' was defined as suspected First Hour Quintet (FHQ) (cardiac arrest, chest pain, stroke, difficulty breathing, trauma). The association of age, sex, and hospitalization history with adverse outcomes was examined using logistic regression. The predictive ability was assessed via area under the curve (AUC) and Hosmer-Lemeshow tests. Of 59,943 patients (median age 63 years, 45% female), 44-45.5% had at least one chronic condition, 3880 (6.47%) died the day or the day after (primary outcome) calling 112. Age 30-59 was associated with increased adjusted odds ratio (OR) of death on day 1 of 3.59 [2.88-4.47]. Male sex was associated with an increased adjusted OR of death on day 1 of 1.37 [1.28-1.47]. Previous hospitalization with nutritional deficiencies (adjusted OR 2.07 [1.47-2.92]) and severe chronic liver disease (adjusted OR 2.02 [1.57-2.59]) was associated with a higher risk of death. For trauma patients, the discriminative ability of the model showed an AUC of 0.74 for death on day 1. Increasing age, male sex, and hospitalization history was associated with increased risk of death on day 1 for FHQ 112 callers. Additional efforts are warranted to clarify the role for risk prediction tools in emergency medical dispatch.

The Role of Ceramide in the Pathogenesis of Alcoholic Liver Disease.

Ceramide is an important second messenger in the sphingomyelin signaling pathway. In this review, we will focus on the potential role of ceramide in the pathogenesis of alcoholic liver disease (ALD). We have summarized the relevant studies and reviews about the role of ceramide in ALD. In addition, we have discussed the role of acid sphingomyelinase and protein phosphatase 2A in ALD, which are associated with ceramide and hepatic steatosis. Recent studies have proved that the immunoreactivity and content of ceramide were increased, both in experimental models of chronic alcohol-induced steatohepatitis and human livers with severe chronic alcohol-related liver disease. Consistent with that, the levels of protein phosphatase 2A and acid sphingomyelinase were increased. Of relevance, the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) was inhibited, which could block the fatty acid oxidation and promote its synthesis. It was hypothesized that ethanol promoted ceramide accumulation and increased PP2A activity by activating ASMase, which may be an important mechanism in the inhibitory effect on AMPK phosphorylation and then contributed to the progression of steatosis. ASMase, a specific mechanism of ceramide generation, was proved to be a regulator of steatosis, fibrosis, lipotoxicity and endoplasmic reticulum stress.

Outcomes of transcatheter aortic valve replacement in patients with chronic liver disease.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to high-risk surgery in patients with comorbid conditions. The role of TAVR in patients with liver disease has not been examined. We examined the procedural and intermediate to long-term follow-up outcomes of patients with severe symptomatic aortic valve stenosis and chronic liver disease, identified by liver biopsy or from a combination of clinical findings. All patients were treated with balloon-expandable transfemoral (TF) or transapical (TA) TAVR between November 2007 and February 2014. A total of 17 of 706 (2.41%) patients treated at our institution with TF [n=14] or TA [n=3] TAVR had chronic liver disease (mean age 77.65±9.06 years, 7 women, mean STS score 8.37, mean Charlson score 5.00, mean MELD score 11.35, Child-Turcotte-Pugh (CTP) Class A [n=11], B [n=6], C [n=0], biopsy proven liver disease [n=5]). Median follow-up was 466 days (range=12-1,403 days). The mean post-procedure length of hospital stay was 5.88±3.08 days. Procedural success was achieved in all cases. In-hospital mortality was 5.88% and 90-day mortality was 17.65%. Safety and efficacy endpoints as defined by the valve academic research consortium (VARC) were significant for one perioperative death from a proximate cardiac cause (post-operative day 14), one death after hospital discharge of unknown cause (post-operative day 12), two late deaths from non-cardiac causes (post-operative days 50 and 487, respectively), and one late death of unknown cause (post-operative day 1,005). There were no life-threatening or major bleeding complications. One patient had an MI, one had a transient ischemic attack, four had transient, Stage I, acute kidney injury and one had transient, Stage II, acute kidney injury. TF and TA TAVR are feasible methods for treating aortic stenosis in patients with chronic liver disease. In patients with mild to moderate chronic liver disease there are acceptable rates of early and late complications, however, outcomes in patients with advanced liver disease (MELD>20 or CTP class C) warrant further study.

Can we expand the indications for laparoscopic liver resection? A systematic review and meta-analysis of laparoscopic liver resection for patients with hepatocellular carcinoma and chronic liver disease.

Liver resection (LR) for patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) poses a high risk of serious postoperative complications and multicentric metachronous lesions requiring repeated treatment. The efficacy of laparoscopic LR (LLR) for such patients has yet to be established. The objective of this study is to test the outcomes of LLR for HCC with the aim of considering potential expansion of the indications for LLR. We performed a systematic review of the pertinent English-language literature. Our search yielded four meta-analyses and 23 comparative studies of LLR for HCC. On the basis of the findings from these studies and our newly conducted meta-analysis, the possibility for expanding the indications for LLR to HCC was examined. The studies show that LLR (vs open) for HCC generally yields better short-term outcomes without compromising long-term outcomes, and that incidences of postoperative ascites and liver failure are decreased with LLR. Several studies show the benefits of LLR for patients with severe CLD and for repeat surgery. Reductions of postoperative ascites and liver failure are among the advantages of LLR. These characteristics of LLR may allow us to expand the indications of LLR to HCC with CLD.

Evaluation of viral load distribution of HBV DNA positive patients at Suleyman Demirel University Hospital

Hepatitis B virus (HBV) may cause a wide spectrum of liver diseases ranging from an asymptomatic carrier state to severe chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). In patients with Chronic hepatitis B (CHB) infection, serum HBV viral load has been shown to be significantly associated with disease activity and disease progression. The aim of this study was to determine the viral load distribution of HBV DNA in patients with HBV infection in Isparta region. Hepatitis B surface antigen (HBs Ag) and HBV DNA levels in serum samples of 1054 patients were analysed retrospectively between January 2013 and December 2013. HBs Ag tests in the serum of patients were measured with chemiluminescence method (Vitros, Johnson&Johnson, USA). The levels of sera HBV DNA were quantified with real-time PCR method by Cobas/AmpliPrep/ Cobas Taqman HBV test v 2.0 (Roche Diagnostics GmbH, Mannheim, Germany) and HBV Quantification Kit v1, Magnesia 16, Montania 483 (Anatolia Geneworks, Turkey). HBV-DNA levels were determined as 1-102 IU/ml (28.6%), 102-3 IU/ml (32.6 %), 103-4 IU/ml (22.7%), 104-5 IU/ml (7.2%), 105-6 IU/ml (2.4%), 106-7 IU/ml (2.4 %), 107-8 IU/ml (1.5%), 108-9 IU/ml (2.4%), ≥109 IU/ml (0.2%). Amounts of the viral load of HBV DNA positive samples were observed to concentrate around the lower levels (1-105 IU/ml) in Isparta region (91%) which predicted lower risk of progression to HCC.

Liver transplantation

The liver transplant procedure has advanced significantly since the 1960s. It is the only curative treatment for severe chronic liver disease including cirrhosis. In collaboration with the French Biomedicine Agency, a complex protocol is put in place by a multi-disciplinary team. The patient's commitment to the treatment project is essential.

Hepatitis B virus infection in Latin America: a genomic medicine approach.

Hepatitis B virus (HBV) infection is the leading cause of severe chronic liver disease. This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America. Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection. Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America; these strains have historically circulated among the indigenous population. Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans. In contrast, genotypes F, A and D are common in acute and chronic infections among mestizos with Caucasian ancestry. Hepatocellular carcinoma is rare in Mexicans, but it has been associated with genotype F1b among Argentineans. This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America, which contrast with those reported in other regions of the world.