Intra-gastric balloon with lifestyle modification: a promising therapeutic option for overweight and obese patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Data on effects of intra-gastric balloon (IGB) on metabolic dysfunction-associated steatotic liver disease (MASLD) are scarce, in part with contradictory results, and mainly obtained in tertiary care patients with diabetes and other comorbidities. We here explore effects of IGB in patients with MASLD referred to a first-line obesity clinic. METHODS: In this prospective cohort study, patients with at least significant fibrosis (≥ F2) and/or severe steatosis (S3) according to screening transient elastography (FibroScan®) were offered a second FibroScan® after 6 months lifestyle modification with or without IGB (based on patient preference). RESULTS: 50 of 100 consecutively screened patients (generally non-diabetic) qualified for repeated evaluation and 29 (58%) of those had a second FibroScan®. At baseline, at least significant fibrosis was present in 28% and severe steatosis in 91%. IGB was placed in 19 patients (59%), whereas 10 patients (41%) preferred only lifestyle modification (no differences in baseline characteristics between both groups). After 6 months, liver stiffness decreased markedly in the IGB group (median: from 6.0 to 4.9 kPa, p = 0.005), but not in the lifestyle modification only group (median: from 5.5 to 6.9 kPa, p = 0.477). Steatosis improved in both groups, (controlled attenuation parameter values; IGB, mean ± SD: from 328 ± 34 to 272 ± 62 dB/m, p = 0.006: lifestyle modification only, mean ± SD: from 344 ± 33 to 305 ± 43 dB/m: p = 0.006). CONCLUSION: Both steatosis and fibrosis improve markedly in overweight/obese patients with MASLD after 6 months IGB combined with lifestyle modification. Our results warrant further research into long-term effect of IGB in these patients.

Retrieval of chronic hepatitis C patients. A manifesto for action to eliminate hepatitis C in the Netherlands: the CELINE project.

Chronic hepatitis C virus (HCV) infection is a global public health issue, which is associated with high rates of morbidity and mortality. The development of direct acting antivirals (DAAs) has transformed treatment: they offer us highly-effective therapy with superior tolerability compared to interferon-containing regimens. In 2016, the World Health Organization (WHO) therefore adopted several ambitious viral hepatitis elimination targets, aiming for a 90% reduction in new infections and a 65% reduction in mortality by 2030. The ultimate goal is to eliminate HCV completely. It is reasonable that these goals may be achieved in the Netherlands due to the low prevalence of chronic HCV, the availability of DAAs, and excellent healthcare infrastructure. This paper describes a national effort to curtail the HCV epidemic in the Netherlands through an HCV retrieval and linkage to care project (CELINE: Hepatitis C Elimination in the Netherlands).

Strategies for achieving viral hepatitis C micro-elimination in the Netherlands.

The Netherlands is striving to achieve national elimination of the hepatitis C virus (HCV) as one of the first countries worldwide. The favorable HCV epidemiology with both low prevalence and incidence, together with access to care and treatment, present excellent conditions to further build on towards this objective. The Dutch national plan on viral hepatitis, introduced in 2016, defines targets in the HCV healthcare cascade and provides a structural framework for the development of elimination activities. Since many different stakeholders are involved in HCV care in the Netherlands, focus has been placed on micro-elimination initiatives as a pragmatic and efficient approach. These numerous micro-eliminations projects have brought the Netherlands closer to HCV elimination. In the near future, efforts specifically have to be made in order to optimize case-finding strategies and to successfully accomplish the nationwide implementation of the registration and monitoring system of viral hepatitis mono-infections, before this final goal can be reached. The upcoming years will then elucidate if the Dutch' hands on approach has resulted in sufficient progress against HCV and if the Netherlands will lead the way towards nationwide HCV elimination.

Ribavirin steady-state plasma level is a predictor of sustained virological response in hepatitis C-infected patients treated with direct-acting antivirals.

BACKGROUND: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. AIM: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). METHODS: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. RESULTS: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL). CONCLUSION: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.

How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Low serum hyaluronic acid levels associated with spontaneous HBsAg clearance.

PURPOSE: The pathophysiological underlying mechanism of spontaneous HBsAg clearance in hepatitis B virus (HBV) infected patients is largely unknown. However, serum hyaluronic acid (sHA) plays a role in liver fibrosis progression and reversely could serve as a potential biomarker for HBsAg clearance. This study investigates whether low sHA is associated with HBsAg loss in non-Asian HBV patients. METHODS: Non-Asian women living in Amsterdam with known chronic HBV infection between 1990-2003 were invited for a single follow-up visit at the Municipal Health Service Amsterdam between September 2011 to May 2012. Serum hyaluronic acid and liver stiffness measurement together with clinical evaluation, biochemical and virologic blood tests were performed. RESULTS: Of the 160 women, HBsAg loss occurred in 38 (23 %) patients between diagnosis and follow-up. sHA levels were lower in HBsAg negative patients compared to HBsAg positive patients (14.5 [9.4-27.2] ng/mL vs 25.0 [12.3-42.5] ng/mL, p <0.01). A similar distinction in sHA between low and high HBV DNA was noted. sHA had a significant discriminatory ability to differentiate between HBsAg positive and HBsAg negative patients, (AUC 0.65 [95 % CI 0.55-0.75], p < 0.01). In multivariable analysis only sHA level was associated with HBsAg loss (OR 0.4 [0.2-0.9]). Finally, F3-F4 fibrosis (cut-off >8.1 kPa) was diagnosed in 3 % in HBsAg negative patients compared to 10 % in HBsAg positive patients (p = 0.15). CONCLUSION: Serum HA levels are lower in patients who experience spontaneous HBsAg loss compared to HBsAg positive patients.

HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1.

The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.

Historic and current hepatitis B viral DNA and quantitative HBsAg level are not associated with cirrhosis in non-Asian women with chronic hepatitis B.

BACKGROUND: Some studies done in Asian patients have shown that serum levels of hepatitis B virus (HBV) DNA predict the development of cirrhosis. However, it is unclear whether this also applies for non-Asian patients. This study investigated historic and current HBV DNA and quantitative hepatitis B surface antigen (HBsAg) levels as predictors of cirrhosis in non-Asian women with chronic HBV. METHODS: A retrospective cohort study of non-Asian women with chronic HBV was performed. Among other variables, HBV DNA and quantitative HBsAg levels were measured in stored historic serum samples obtained during pregnancy (period 1990-2004) and current serum samples (period 2011-2012) to determine any association with liver cirrhosis by liver stiffness measurement (LSM). RESULTS: One hundred and nineteen asymptomatic, treatment-naïve non-Asian women were included; the median number of years between the historic sample and the current sample was 17 (interquartile range (IQR) 13-20). The median historic log HBV DNA and quantitative log HBsAg levels were 2.5 (IQR 1.9-3.4) IU/ml and 4.2 (IQR 3.6-4.5) IU/ml, respectively. LSM diagnosed 14 patients (12%) with F3-F4 fibrosis, i.e. stiffness >8.1kPa. No association of cirrhosis was found with historic HBV DNA (relative risk (RR) 0.34, 95% confidence interval (CI) 0.05-2.44) or with the quantitative HBsAg level (HBsAg level >1000 IU/ml, RR 0.35, 95% CI 0.11-1.11). Multivariable analysis identified alcohol consumption (odds ratio (OR) 6.4, 95% CI 1.3-30.1), aspartate aminotransferase >0.5 times the upper limit of normal (OR 15.4, 95% CI 1.9-122.6), and prothrombin time (OR 12.0, 95% CI 1.2-120.4), but not HBV DNA or quantitative HBsAg level, to be independent predictors of the presence of cirrhosis. CONCLUSIONS: Neither historic nor current HBV DNA or the quantitative HBsAg level is associated with the development of HBV-related cirrhosis in non-Asian women.

ELF-test less accurately identifies liver cirrhosis diagnosed by liver stiffness measurement in non-Asian women with chronic hepatitis B.

BACKGROUND: The enhanced liver fibrosis test (ELF-test) has been validated for several hepatic diseases. However, its performance in chronic hepatitis B virus (CHB) infected patients is uncertain. OBJECTIVE: This study investigates the diagnostic value of the ELF test for cirrhosis identified by liver stiffness measurement (LSM) in non-Asian women with CHB. STUDY DESIGN: Women of non-Asian origin with perinatally acquired CHB infection, detected during pregnancy in the period 1990-2003, returned to our center between September 2011 and May 2012 for LSM and blood sampling to perform an ELF test and to calculate, APRI and FIB-4 scores. Fibrosis stages were classified by the METAVIR system. RESULTS: A total of 119 women were included in this study with a median age of 43 years, all ALT levels being <2× ULN and all being HBeAg negative. The overall median LSM (IQR) stiffness and ELF test were 5.5kPa (4.0-6.8) and 8.4 (7.8-9.2) respectively. LSM and ELF test classified 14 (12%) and 19 (16%) patients with severe fibrosis to cirrhosis (≥F3, i.e. liver stiffness >8.1kPa), however in only 4 (3%) patients there was an agreement between LSM and ELF test. With LSM as reference, the area under receiver operating characteristic curve (AUROC) for detection of ≥F3 fibrosis was for ELF 0.65 (95% CI 0.51-0.80; p=0.06), APRI 0.66 (0.50-0.82; p=0.07) and FIB-4 0.66 (0.49-0.82; p=0.07). CONCLUSION: The ELF test less accurately discriminates severe fibrosis or cirrhosis when compared to LSM in our cohort of non-Asian women with CHB.

Dutch guidance for the treatment of chronic hepatitis C virus infection in a new therapeutic era.

BACKGROUND: A new era for the treatment of chronic hepatitis C is about to transpire. With the introduction of the first-generation protease inhibitors the efficacy of hepatitis C treatment improved significantly. Since then, the therapeutic agenda has moved further forward with the recent approval of sofosbuvir and the expected approval of agents such as simeprevir and daclatasvir. This paper, developed parallel to the approval of sofosbuvir, is to serve as a guidance for the therapeutic management of chronic hepatitis C. METHODS: We performed a formal search through PubMed, Web of Science and ClinicalTrials.gov to identify all clinical trials that have been conducted with EMA-approved new agents in hepatitis C; for this version (April 2014) we focused on sofosbuvir. For each disease category, the evidence was reviewed and recommendations are based on GRADE. RESULTS: We identified 11 clinical trials with sofosbuvir and for each disease category recommendations for treatment are made. Not all disease categories were studied extensively and therefore in some cases we were unable to provide recommendations. CONCLUSION: The recent approval of sofosbuvir will most likely change the therapeutic landscape of chronic hepatitis C. The use of sofosbuvir-containing regimens can shorten the duration of therapy, increase efficacy and result in less side effects, compared with standard of care. The efficacy relative to standard of care needs to be weighed against the increased costs of sofosbuvir. With future approval of the other direct-acting antivirals, the outcome of hepatitis C treatment will likely improve further and this guidance will be updated.

Hepatocellular carcinoma: Dutch guideline for surveillance, diagnosis and therapy.

UNLABELLED: Hepatocellular carcinoma (HCC) is rare in the Netherlands, even though the incidence has increased quite sharply in recent years. Standard treatment options consist of surgery, orthotopic liver transplantation, radiofrequency ablation, transarterial chemoembolisation (TACE) and systemic therapy with sorafenib. The consensus-based Dutch HCC guideline, established in 2013, serves to guide surveillance, diagnosis and treatment options: Surveillance should be performed by ultrasound at six-month intervals in well-defined cirrhotic patients and in selected high-risk hepatitis B carriers; A nodule > 1 cm in cirrhotic patients with arterial hypervascularity and venous or delayed phase washout at four-phase CT or MRI scan establishes the diagnosis of HCC; In patients with HCC without underlying cirrhosis, resection should be considered regardless of tumour size; In cirrhotic HCC patients, tumour stage, severity of underlying cirrhosis, and performance status determine treatment options. The algorithm of the Barcelona Clinic Liver Cancer (BCLC) staging system should be followed; Patients with Child-Pugh A-B cirrhosis (CP < 8 points) and performance status 0-2 are candidates for any active treatment other than transplantation; In early stage HCC (BCLC stage 0 or A, compensated cirrhosis without portal hypertension) surgical resection, liver transplantation, or radiofrequency ablation should be considered; In intermediate stage HCC (BCLC stage B) TACE and÷ or radiofrequency ablation should be considered; In advanced stage HCC (BCLC stage C) sorafenib should be considered. CONCLUSION: The Dutch HCC guideline offers advice for surveillance, diagnosis and treatment of HCC.

The 2012 revised Dutch national guidelines for the treatment of chronic hepatitis B virus infection.

In 2008, the Netherlands Association of Gastroenterologists and Hepatologists (Nederlands Vereniging van Maag-Darm-Leverartsen) published the Dutch national guidelines for the treatment of chronic hepatitis B virus infection. New insights into the treatment of chronic hepatitis B with relevance for clinical practice have been adopted in these concise, revised guidelines. The most important changes include the choice of initial antiviral therapy, licensing of tenofovir for the treatment of chronic hepatitis B and the management of antiviral resistance.

Real-life costs of hepatitis C treatment.

BACKGROUND: Hepatitis C virus infection is a serious health threat in today's society. Improved identification strategies have increased the number of patients undergoing the expensive treatment with ribavirin and peg-interferon, inducing a substantial economic burden. METHODS: In a retrospective cohort study in three treatment centres in the Netherlands, files of patients treated between 2001 and 2010 were systematically searched for all cost-inducing treatment details. Costs of treatment resulting in sustained viral response (SVR), relapse, non-response and the costs per cured patient were specified for genotype and treatment setting. Determinants of costs were determined by multivariate linear regression. RESULTS: The mean 'real-life' treatment costs excluding side effects for genotype 1/4 and genotype 2/3 were approximately € 12,900 and € 9900 for all patients, € 15,500 and € 10,100 for treatment resulting in SVR and € 16,800 and € 12,100 for relapse, respectively. Costs per cured patient were € 28,500 and € 15,400 respectively. The costs of non-response were approximately € 8000 for all genotypes. Costs of side effects can be high and are mainly caused by incidental treatment for neutropenia. Medication is the main component of treatment costs. Treatment costs were higher in the academic setting due to longer duration and higher costs of side effects. Regression analysis confirms duration as the main determinant of treatment costs excluding side effects. CONCLUSION: The 'real-life' costs of treatment are mainly determined by treatment duration, medication costs and costs of side effects. The costs of unsuccessful treatment are considerable as are the costs of side effects. Therefore, future research should aim at increasing SVR rates, reducing treatment duration and preventing side effects.

Ribavirin rather than PEG-interferon pharmacodynamics predict nonresponse to antiviral therapy in naive chronic hepatitis C patients.

Twenty to fifty per cent of patients with chronic hepatitis C (CHC) experience nonresponse to current antiviral therapy, which may relate in part to ribavirin or PEG-interferon pharmacodynamics. We evaluated potential relevance of various factors for nonresponse. Two hundred forty-two naive CHC patients who received in a previous trial at least 24 weeks of antiviral therapy, including PEG-interferon alfa-2b and ribavirin, were analysed. Of them, 53% were infected with hepatitis C virus (HCV) genotype 1-4, 71% exhibited high viral load and 32% had severe fibrosis/cirrhosis. After 24 weeks of treatment, 39 patients (16%) were nonresponders. In multivariate analysis, lower serum ribavirin concentrations, HCV genotype 1-4 and higher baseline γ-GT predicted nonresponse. Week-24 ribavirin concentrations (2.2 vs 2.8 mg/L, P < 0.001), average ribavirin doses (14.5 vs 15.2 mg/kg per day, P = 0.03) and week-24 haemoglobin decreases (1.7 vs 2.0 mm, P = 0.02) were lower in nonresponders. Nonresponse rates increased progressively at decreasing ribavirin concentrations: 4%, 11%, 13% and 36% in case of serum ribavirin concentrations ≥4, 3-4, 2-3 and ≤2 mg/L, respectively (P = 0.001). Ribavirin concentrations correlated with both week-24 haemoglobin decreases (r = 0.42, P < 0.001) and ribavirin doses (r = 0.17, P = 0.01). Subgroup analysis in HCV genotype 1-4 patients revealed essentially the same results. Nonresponse was exceptional in HCV genotype 2-3 patients and associated with ribavirin concentrations <2 mg/L. Presumed interferon-related factors (average PEG-interferon doses and decreases in leucocytes, granulocytes, platelets and body weight) did not differ between nonresponders and responders. In conclusion, ribavirin- rather than PEG-interferon-related factors are independent and potentially modifiable predictors of nonresponse in treatment-naive CHC patients.

Beneficial effect of successful HCV treatment in patients with inherited bleeding disorders, assessed by liver stiffness measurements.

Hepatitis C infection is a major comorbidity in patients with inherited bleeding disorders. Successful antiviral treatment leads to a reduction in liver fibrosis, as shown by liver biopsies. Liver stiffness measurement (LSM) is a non-invasive method of assessing liver fibrosis. The aim of this cohort study was to evaluate the long-term effect of successful antiviral treatment, using LSM, in HCV-infected patients with inherited bleeding disorders. The LSM were performed in 2005 (LSM 1) and 2009 (LSM 2) in 39 patients who were successfully treated for HCV. The change in liver fibrosis between LSM 1 and 2 was assessed. The median duration of HCV infection was 28.8 years. A total of 22 patients (56%) underwent successful antiviral treatment before LSM 1 (group 1), and 17 patients between LSM 1 and LSM 2 (group 2). The median time since antiviral treatment was 8.8 years in group 1 and 2.5 years in group 2. In group 1, the median results of LSM 1 and 2 were similar (6.0 vs. 5.6 kPa, P-value 0.36), so overall, patients remained stable. In three patients in this group, all treated more than 15 years ago, an increase of liver stiffness was shown. Group 2 showed a significant improvement in median LSM results (10.3 vs. 6.1 kPa, P-value <0.01), with decrease of liver stiffness in 82%. Even after a long HCV infection duration, successful antiviral treatment led to a significant improvement of fibrosis, measured by LSM, mainly in the first few years after completing treatment.

The role of mycophenolate mofetil in the management of autoimmune hepatitis and overlap syndromes.

BACKGROUND: Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second line treatment. AIM: To assess the efficacy of mycophenolate mofetil as second line treatment after AZA-intolerance or AZA-nonresponse in autoimmune hepatitis and overlap syndromes. METHODS: Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA-intolerance or AZA-nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression. RESULTS: Forty-five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA-nonresponse group compared to 67% and 0% in the AZA-intolerance group (P = 0.008). In overlap-syndromes remission or response was reached in 57% and 14% in the AZA-nonresponse group and 63% and 25% of the AZA-intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA-nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA-nonresponse group (P < 0.001). CONCLUSIONS: Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine-intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.

Liver stiffness measurements to assess progression of fibrosis in HCV-infected patients with inherited bleeding disorders.

Hepatitis C is a major co-morbidity in patients with inherited bleeding disorders, leading to progressive liver fibrosis and eventually cirrhosis. Liver stiffness measurement (LSM) is a non-invasive way of assessing the extent of liver fibrosis. This article describes our experience with serial LSM to assess prospectively progression of fibrosis in a cohort of patients with inherited bleeding disorders and chronic hepatitis C. A total of 84 patients underwent serial LSMs, with a median interval of 3.7 years. The change in LSM results over time was assessed. Overall, there was no significant difference between the median results of LSM 1 and LSM 2. The median result of LSM 2 was low (6.6 kPa), after a median duration of infection of 37 years. On the individual level, deterioration of LSM results of more than 2 kPa was seen in 13 patients (16%), 44 patients (52%) remained stable and 27 patients (32%) showed improvement of LSM results of more than 2 kPa. These results are comparable with those of paired liver biopsy studies. LSM appears to be a good alternative for liver biopsies in patients with hepatitis C and inherited bleeding disorders, although the interpretation of the unexpected improvement we found in some of our patients is not straightforward. LSMs will be repeated in our patient population in a few years to be able to better assess the value of serial LSM.