Natural history of hepatitis C Westbrook, Rachel H; Dusheiko, Geoffrey
Journal of hepatology,
11/2014, Letnik:
61, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and ...hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Accurate studies of the time course for clearance of acute hepatitis C are difficult to carry out because of the silent onset of the acute disease. The likelihood of spontaneous HCV resolution is associated with several genetic factors, including IL28B inheritance and the DQB1∗ 0301 allele of the major histocompatibility complex class II. Most data suggest that resolution in the acute phase without progression to chronic disease is not accompanied by significant disease, but minor histological lesions have been observed in anti-HCV positive, HCV RNA negative individuals. The risk of reinfection remains a possibility after clearance of acute hepatitis C. High rates of sexually-transmitted infection are being reported in HIV positive men who have sex with men (MSM). Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10–20% of patients over 20–30 years of HCV infection. However, the published data indicate varying progression rates to cirrhosis. Overall, once cirrhosis has developed there is a 1–5% annual risk of HCC and a 3–6% annual risk of hepatic decompensation. Following an episode of decompensation the risk of death in the following year is between 15% and 20%. The high number of chronically infected individuals, the burden of disease, and the absence of a vaccine indicates that treatment will form part of the disease control but the impact, effectiveness and outcomes of treatment in various groups remain uncertain. Several studies and meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage, but the risk is not eliminated.
Pregnancy associated liver diseases affect up to 3% of pregnant women and are the most frequent cause of liver dysfunction in pregnancy. When severe, they are associated with significant morbidity ...and mortality for both mother and infant. A rapid evaluation to distinguish them from non-pregnancy related liver dysfunction is essential, in order to facilitate appropriate management. Liver disease unrelated to pregnancy can present de novo in pregnancy, or pregnancy can occur in women with preexisting liver pathology (Table 1). Research and subsequent advances in medical care have resulted in improved but still not satisfactory maternal and fetal outcomes. In this review we provide an overview of the liver diseases specific to the pregnant state and an update on their pathogenesis, treatment and outcomes. The risks of pregnancy in women with pre-existent liver pathology is detailed and recent advances in our understanding of specific risks and outcomes are discussed.
Patients with compensated advanced chronic liver disease (cACLD) can safely avoid screening endoscopy with a platelet count >150 × 109 cells/L and a liver stiffness measurement (LSM) <20 kPa (Baveno ...VI criteria). However, the total number of avoided endoscopies using this rule is relatively low. We aimed at expanding the Baveno VI criteria and validating them in additional cohorts. Patients from the Anticipate cohort (499 patients with cACLD of different etiologies) were used to study the performance of different thresholds of platelets and LSM for the identification of patients at very low risk (<5%) of having varices needing treatment (VNT). The new criteria (Expanded‐Baveno VI) were validated in two additional cohorts from London (309 patients) and Barcelona (117 patients). The performance of the new criteria by etiology of cACLD was also assessed. The best new expanded classification rule was platelet count >110 × 109 cells/L and LSM <25 kPa. This was validated in the two additional cohorts. Overall, the Expanded‐Baveno VI criteria would potentially spare 367 (40%) endoscopies (21% with Baveno VI criteria) with a risk of missing VNT of 1.6% (95% confidence interval, 0.7%‐3.5%) in patients within the criteria and 0.6% (95% confidence interval, 0.3%‐1.4%) in the overall population of 925 patients evaluated. The Expanded‐Baveno VI criteria performed well in patients with cACLD with hepatitis C virus and alcoholic and nonalcoholic steatohepatitis. Conclusion: The new Expanded‐Baveno VI criteria spare more endoscopies than the original criteria with a minimal risk of missing VNT in most of the main etiologies of cACLD. (Hepatology 2017;66:1980–1988)
Summary Severe liver disease in pregnancy is rare. Pregnancy-related liver disease is the most frequent cause of liver dysfunction in pregnancy and provides a real threat to fetal and maternal ...survival. A rapid diagnosis differentiating between liver disease related and unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. Research has improved our understanding of the pathogenesis of pregnancy-related liver disease, which has translated into improved maternal and fetal outcomes. Here, we provide an overview of liver diseases that occur in pregnancy, an update on the key mechanisms involved in their pathogenesis, and assessment of available treatment options.
Background & Aims No standardised definition exists for acute, severe AIH (AS-AIH). However, rapid identification of AS-AIH and early corticosteroid therapy may prevent the need for liver ...transplantation (LT). We set out to determine the clinical outcomes of patients with AS-AIH presenting to our institution with particular focus on the role of corticosteroids. Methods Retrospective analysis of a prospectively collated database identified patients presenting with AS-AIH from 1999 to 2009. We defined AS-AIH as an acute presentation with an INR of ⩾1.5 at any time without histological evidence of cirrhosis. Results 32 patients were identified with AS-AIH. Among the 32 AS-AIH patients 23 were treated with corticosteroids of whom 10 (48%) required LT, whilst all 9 untreated patients required LT ( p = 0.01). Untreated patients demonstrated higher MELD scores at presentation (34 vs. 28 p = 0.01) and a non-significant decrease in episodes of sepsis but no difference in sepsis or mortality was observed between untreated or treated patients (11% vs. 26% p = 0.6 and 22% vs. 17% p = 0.99 respectively). Among treated patients, no difference in MELD scores was observed between responders or failures. Despite 59% undergoing LT, six deaths (19%) occurred. Conclusion In a well characterised cohort of patients with AS-AIH, almost 60% required LT and 20% died. There was no difference in prognostic scores between steroid responders and failures and steroid exposure did not appear to jeopardise survival. Patients with AS-AIH should be considered for a trial of corticosteroids expediently whilst a thorough search for sepsis and assessment for LT should occur if clinical deterioration or encephalopathy develops.
Pregnancy-specific liver diseases Katarey, Dev; Westbrook, Rachel H.
Best practice & research. Clinical obstetrics & gynaecology,
10/2020, Letnik:
68
Journal Article
Recenzirano
Liver disease presenting in pregnancy may be due to a pregnancy-specific liver disorder, due to previously unrecognised pre-existing liver disease, or de novo liver disorders coincidentally ...presenting in a pregnant woman. The pregnancy-specific liver diseases can span from mild disease with limited impact on maternal and foetal health to severe disorders that can result in significant morbidity and mortality for mother and foetus. Swift identification of these disorders is essential to allow timely and appropriate management via a multi-disciplinary approach. The pregnancy-specific conditions, including their presentation, investigations, and management are reviewed in this chapter in detail.
•Pregnancy-specific liver diseases (PSLD) are relatively common.•PSLD rarely causes significant liver pathology, but acute liver failure can occur.•PSLD more commonly has adverse effects on foetal and non-liver maternal outcomes.•In late trimester PSLD, consider whether early delivery is necessary.
Human leukocyte antigen (HLA) matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit; however, the impact of HLA mismatching remains uncertain. We ...explored the effect of class I and II HLA mismatching on graft failure and mortality. A total of 1042 liver transplants performed at a single center between 1999 and 2016 with available HLA typing data were included. The median follow‐up period was 9.38 years (interquartile range 4.9–14) and 350/1042 (33.6%) transplants resulted in graft loss and 280/1042 (26.9%) in death. Graft loss and mortality were not associated with the overall number of mismatches at HLA‐A, HLA‐B, HLA‐C, HLA‐DR, and HLA‐DQ loci. However, graft failure and mortality were both increased in HLA mismatching on graft failure and mortality the presence of one (p = 0.004 and p = 0.01, respectively) and two (p = 0.01 and p = 0.04, respectively) HLA‐A mismatches. Elevated hazard ratios for graft failure and death were observed with HLA‐A mismatches in univariate and multivariate Cox proportional hazard models. Excess graft loss with HLA‐A mismatch (138/940 14.7% mismatched compared with 6/102 5.9% matched transplants) occurred within the first year following transplantation (odds ratio 2.75; p = 0.02). Strikingly, transplants performed at a single all grafts lost due to hepatic artery thrombosis were in HLA‐A–mismatched transplants (31/940 vs. 0/102), as were those lost due to sepsis (35/940 vs. 0/102). In conclusion, HLA‐A mismatching was associated with increased graft loss and mortality. The poorer outcome for the HLA‐mismatched group was due to hepatic artery thrombosis and sepsis, and these complications occurred exclusively with HLA‐A–mismatched transplants. These data suggest that HLA‐A mismatching is important for outcomes following liver transplant. Therefore, knowledge of HLA‐A matching status may potentially allow for enhanced surveillance, clinical interventions in high‐risk transplants or stratified HLA‐A matching in high‐risk recipients.
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