Hepatic Decompensation Events Research Articles

Liver Fibrosis Progression in Hepatitis C Virus Infection After Seroconversion

Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions. To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection. Secondary data analysis of persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline. Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation. The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P < .001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%). Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.

Long-term survival and liver-related events after pegylated interferon/ribavirin therapy in HIV-infected patients with chronic hepatitis C.

Sustained HCV clearance after hepatitis C therapy is associated with reduced liver-related complications and death. It is unknown if treatment may provide any clinical benefit in patients that fail therapy. This could be particularly relevant in HIV-HCV-coinfected patients, in whom liver disease progresses more rapidly. This was a retrospective study of clinical end points in a large cohort of HIV-HCV-coinfected patients with compensated liver disease followed since 2004. Patients were stratified into three groups: treated and cured, treatment failures and non-treated. Follow-up ended at the time of last visit, first liver decompensation event or death. A total of 527 HIV-HCV-coinfected patients were examined, of whom 339 (64.3%) had been treated with pegylated interferon/ribavirin. During a mean follow-up of 70.5 months, hepatic decompensation events or liver-related deaths occurred less frequently in cured patients (4/138; 2.9%) than in treatment failures (28/201; 13.9%) or untreated (25/188; 13.3%) patients (P<0.001). Interestingly, in the subset of patients with baseline advanced liver fibrosis (Metavir F3-F4), those with treatment failure experienced less hepatic decompensation events or deaths than untreated patients (19% versus 42%; P=0.005) and this finding was more pronounced in patients harbouring IL28B-CC alleles (15.8% versus 47.4%; P=0.02). Sustained HCV clearance following pegylated interferon/ribavirin therapy is associated with a reduced incidence of liver complications and death in HIV-HCV-coinfected patients. In the subset of patients with baseline advanced liver fibrosis, treatment provides clinical benefit despite lack of sustained virological response. The transient antiviral and/or anti-inflammatory effect of interferon, more recognizable in IL28B-CC carriers, could explain this finding.

Eltrombopag: a review of its use in the treatment of thrombocytopenia in patients with chronic hepatitis C.

Eltrombopag (Revolade(®); Promacta(®)) is an orally bioavailable, small-molecule, thrombopoietin receptor agonist that selectively binds to thrombopoietin receptors on megakaryocyte precursors and megakaryocytes leading to increased platelet production. It is approved in a number of countries for the treatment of thrombocytopenia, including adult patients with chronic hepatitis C virus (HCV) infection to allow for the initiation and maintenance of peginterferon-based therapy, which is the focus of this review. In two, well-designed, randomized controlled trials in adults with chronic HCV infection and thrombocytopenia (ENABLE-1 and ENABLE-2), eltrombopag increased platelet counts to sufficient levels to allow for the initiation of peginterferon-based antiviral therapy in 95 % of patients whose baseline platelet counts would have made them ineligible or marginal candidates for peginterferon therapy. Moreover, a significantly higher proportion of eltrombopag recipients than placebo recipients achieved a sustained virological response (primary endpoint) 24 weeks after the completion of antiviral therapy. Of note, the additional benefit over placebo was relatively small (<10 %). Compared with placebo, eltrombopag was associated with fewer patients discontinuing antiviral therapy early and a numerically greater proportion of patients not requiring antiviral dose reduction. Oral eltrombopag had an acceptable tolerability profile; however, there is an increased risk of adverse events, including potentially fatal hepatic decompensation and thromboembolic events. Eltrombopag provides a new treatment option for thrombocytopenia in patients with chronic HCV infection to allow for optimal antiviral therapy.

Safety profile of boceprevir and telaprevir in chronic hepatitis C: Real world experience from HCV-TARGET

The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated. In 90 medical centres, patients with chronic HCV received pegylated interferon, ribavirin, and either telaprevir or boceprevir per local standard of care. Demographic, adverse event, clinical, and virological data were collected during treatment and follow-up. A total of 2084 patients (97% HCV genotype 1) received at least one dose of a protease inhibitor. At baseline, 38% of patients had cirrhosis, and 57% had received at least one prior treatment for hepatitis C. Serious adverse events occurred in 12% of patients receiving protease inhibitor therapy. Overall, 66% of patients experienced anaemia, leading to frequent ribavirin dose reductions (42%) and erythropoietin use (37%); 11% received blood transfusion. More than 90% of patients had adverse events that led to a prescription, treatment, or dosage change, and 39% of patients discontinued treatment early, most commonly because of adverse events (18%) or lack of efficacy (16%). Hepatic decompensation events occurred in 3% of all patients. Age, female gender, cirrhosis, HCV genotype 1 subtype, creatinine clearance, platelet levels, albumin levels and haemoglobin levels were independent predictors of anaemia. Five deaths occurred. Overall, 52% of all patients achieved a sustained virologic response. In academic and community centres, where chronic hepatitis C patients commonly have advanced liver disease, triple therapy was associated with a high rate of adverse events and involved frequent treatment modifications and adverse event management.

Liver fibrosis progression despite HCV cure with antiviral therapy in HIV-HCV-coinfected patients.

Accelerated liver fibrosis and more frequent hepatic decompensation events and liver-related deaths are characteristically seen in chronic hepatitis C patients coinfected with HIV compared with HCV-monoinfected individuals. Quantitative estimates of long-term clinical benefits derived from curing HCV with antiviral therapy in coinfected patients are scarce, despite being needed for accurate cost-effectiveness decisions using expensive direct-acting antivirals in this population. We retrospectively examined all HIV-HCV-coinfected patients followed at one reference clinic in Madrid since 2004. Liver fibrosis was measured longitudinally using elastometry; changes above 30% in kilopascal units were considered as significant. A total of 568 HIV-HCV-coinfected patients were examined. Pegylated interferon/ribavirin therapy had been given to 396 (69.7%) of whom 138 (34.8%) had achieved sustained virological response (SVR). Mean follow-up was of 6.8 (±1.5) years for hepatic events and 4.4 (±0.8) years for liver fibrosis. Hepatic decompensation events, liver-related deaths and significant liver fibrosis progression occurred less frequently in SVR than in non-treated/treatment failures. Although regression of liver fibrosis occurred in most SVR patients, fibrosis significantly progressed in 7.2% of them, in association with higher plasma HIV RNA (P=0.005) and longer exposure to HIV protease inhibitors (P=0.009). Achievement of SVR dramatically reduces the risk of hepatic decompensation events and liver-related deaths in HIV-HCV-coinfected patients. Although liver fibrosis generally improves following HCV cure, worsening may occur in association with uncontrolled HIV replication and prolonged exposure to protease inhibitors. Thus, periodic assessment of liver fibrosis is warranted after SVR and screening for liver cancer should continue in coinfected patients with advanced liver fibrosis.

Association of Distance From a Transplant Center With Access to Waitlist Placement, Receipt of Liver Transplantation, and Survival Among US Veterans

Centralization of specialized health care services such as organ transplantation and bariatric surgery is advocated to improve quality, increase efficiency, and reduce cost. The effect of increased travel on access and outcomes from these services is not fully understood. To evaluate the association between distance from a Veterans Affairs (VA) transplant center (VATC) and access to being waitlisted for liver transplantation, actually having a liver transplant, and mortality. Retrospective study of veterans meeting liver transplantation eligibility criteria from January 1, 2003, until December 31, 2010, using data from the Veterans Health Administration's integrated, national, electronic medical record linked to Organ Procurement and Transplantation Network data. The primary outcome was being waitlisted for transplantation at a VATC. Secondary outcomes included being waitlisted at any transplant center, undergoing a transplantation, and survival. From 2003-2010, 50,637 veterans were classified as potentially eligible for transplant; 2895 (6%) were waitlisted and 1418 of those were waitlisted (49%) at 1 of the 5 VATCs. Of 3417 veterans receiving care at a VA hospital located within 100 miles from a VATC, 244 (7.1%) were waitlisted at a VATC and 372 (10.9%) at any transplant center (VATC and non-VATCs). Of 47,219 veterans receiving care at a VA hospital located more than 100 miles from a VATC, 1174 (2.5%) were waitlisted at a VATC and 2523 (5.3%) at any transplant center (VATC and non-VATCs). In multivariable models, increasing distance to closest VATC was associated with significantly lower odds of being waitlisted at a VATC (odds ratio [OR], 0.91 [95% CI, 0.89-0.93] for each doubling in distance) or any transplant center (OR, 0.94 [95% CI, 0.92-0.96] for each doubling in distance). For example, a veteran living 25 miles from a VATC would have a 7.4% (95% CI, 6.6%-8.1%) adjusted probability of being waitlisted, whereas a veteran 100 miles from a VATC would have a 6.2% (95% CI, 5.7%-6.6%) adjusted probability. In adjusted models, increasing distance from a VATC was associated with significantly lower transplantation rates (subhazard ratio, 0.97; 95% CI, 0.95-0.98 for each doubling in distance). There was significantly increased mortality among waitlisted veterans from the time of first hepatic decompensation event in multivariable survival models (hazard ratio, 1.03; 95% CI, 1.01-1.04 for each doubling in distance). For example, a waitlisted veteran living 25 miles from a VATC would have a 62.9% (95% CI, 59.1%-66.1%) 5-year adjusted probability of survival from first hepatic decompensation event compared with a 59.8% (95% CI, 56.3%-63.1%) 5-year adjusted probability of survival for a veteran living 100 miles from a VATC. Among VA patients meeting eligibility criteria for liver transplantation, greater distance from a VATC or any transplant center was associated with lower likelihood of being waitlisted, receiving a liver transplant, and greater likelihood of death. The relationship between these findings and centralizing specialized care deserves further investigation.

Hepatitis Delta Is a Major Determinant of Liver Decompensation Events and Death in HIV-Infected Patients

Coinfection with hepatitis viruses is common in individuals infected with human immunodeficiency virus (HIV) and has become a leading cause of complications and death in those receiving antiretroviral therapy (ART). We retrospectively examined the effect of coinfection with hepatitis B, C, and/or D viruses (HBV, HCV, HDV, respectively) on liver decompensation events (ascites, variceal bleeding, encephalopathy, and/or hepatocellular carcinoma) and liver-related mortality in HIV-positive patients on regular follow-up since the year 2004 at a reference HIV clinic in Madrid, Spain. A total of 1147 HIV-infected patients (mean age, 42 years; 81% males; 46% intravenous drug users, 85.4% on ART) were analyzed. Mean follow-up was 81.2 ± 17.8 months. At baseline, 521 patients (45.4%) were HCV-antibody positive, 85 (7.4%) were hepatitis B surface antigen positive, and 17 (1.5%) were anti-HDV positive. A total of 233 HIV/HCV-coinfected patients received antiviral therapy for HCV, of whom 106 (45%) achieved sustained virologic response (SVR). Overall, 15 patients died of liver-related complications and 26 developed hepatic decompensation events. Taking as controls the 524 HIV-monoinfected patients, HDV coinfection (adjusted hazard ratio [AHR], 7.5; 95% confidence interval [CI], 1.84-30.8; P = .005) and baseline liver stiffness (AHR, 1.1; 95% CI, 1.07-1.13; P < .0001) were associated with a higher rate of liver-related morbidity and mortality. In contrast, SVR following hepatitis C therapy in HIV/HCV-coinfected patients was protective (AHR, 0.11; 95% CI, .01-.86; P = .03). Hepatitis delta is associated with a high rate of death and liver decompensation events in HIV-infected patients on ART.

Antiretroviral Therapy Reduces the Rate of Hepatic Decompensation Among HIV- and Hepatitis C Virus–Coinfected Veterans

Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure. We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation. We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI], .54-.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI, .43-.82). Initiation of ART significantly reduced the rate of hepatic decompensation by 28%-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease.

Eltrombopag Increases Platelet Numbers in Thrombocytopenic Patients With HCV Infection and Cirrhosis, Allowing for Effective Antiviral Therapy

Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV. Patients with HCV infection and thrombocytopenia (platelet count <75,000/μL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy. More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/μL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2. Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.

Validation of three coding algorithms to identify patients with end‐stage liver disease in an administrative database

PURPOSE: Use of administrative or population-based databases for post-marketing pharmacoepidemiology research in patients with end-stage liver disease (ESLD) has been limited by the difficulty of accurately identifying such patients. Algorithms to identify patients with ESLD using ICD-9-CM codes have not been developed outside of the Veterans Affairs healthcare setting. METHODS: We queried electronic medical records at two tertiary care hospitals to identify patients with ICD-9-CM codes indicative of ESLD. Coding algorithms were developed to identify patients with confirmed ESLD, and these were tested to determine their positive predictive value (PPV). RESULTS: The presence of one inpatient or outpatient ICD-9-CM code for: (i) cirrhosis; (ii) chronic liver disease, and (iii) a hepatic decompensation event yielded a PPV of 85.2% (167/196; 95% CI: 79.4%-89.9%). The PPV increased to 89.3% (150/168; 95% CI: 83.6%-93.5%) when the algorithm required two or more ICD-9-CM codes for a hepatic decompensation. However, an algorithm requiring only one ICD-9-CM code for (i) cirrhosis and (ii) a hepatic decompensation event, in the absence of a chronic liver disease code, yielded a PPV of 85.7% (30/35; 95% CI: 69.7%-95.2%). CONCLUSIONS: A coding algorithm that includes at least one ICD-9-CM code for cirrhosis plus one ICD-9-CM code for a hepatic decompensation event has a high PPV for identifying patients with ESLD. The inclusion of at least two codes indicative of a hepatic decompensation event increased the PPV. This algorithm can be used in future epidemiologic studies to examine the outcomes of a variety of long-term medical therapies in patients with ESLD. Copyright © 2012 John Wiley & Sons, Ltd.

Validity of diagnostic codes and liver‐related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study

The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS). Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin ≥ 5.0 g/dL, albumin ≤ 2.0 g/dL, INR ≥ 1.7) recorded 1 year before through 6 months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined. Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95%CI, 33%-50%) and 56 (PPV, 28%; 95%CI, 22%-35%) patients, respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95%CI, 47%-79%). One inpatient or ≥2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95%CI, 77%-98%) for confirmed hepatic decompensation events. An algorithm of 1 inpatient or ≥ 2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts.

Frequent hepatitis B virus rebound among HIV–hepatitis B virus-coinfected patients following antiretroviral therapy interruption

The impact of antiretroviral therapy (ART) interruption in HIV-hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study. Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV-positive) participants at baseline, and at months 1, 2, 4, 6, 8, 10, and 12. Among HBV-positive participants in the ART interruption (drug conservation) (n = 72) and ART continuation (virological suppression) (n = 62) arms, HBV DNA rebound of more than 1 log from baseline at months 1-4 was seen in 31-33% (P = 0.003) and 3-4% (P = 0.017), respectively. Thirteen HBV-positive participants had HBV DNA rebound of more than 3 log, including 12 in the drug conservation arm, of which eight were on tenofovir-containing regimens. Factors independently associated with a HBV DNA rebound were drug conservation arm (P = 0.0002), nondetectable HBV DNA at baseline (P = 0.007), and black race (P = 0.03). Time to ART reinitiation was shorter (7.5, 15.6, and 17.8 months; P < 0.0001) and proportion reinitiating greater (62.5, 46.5, and 39.7%; P = 0.0002) among HBV-positive participants as compared with hepatitis C virus-positive and non-HBV/hepatitis C virus participants in the drug conservation arm. No hepatic decompensation events occurred among HBV-positive participants in either arm. HBV DNA rebound following ART interruption is common and may be associated with accelerated immune deficiency in HIV-HBV-coinfected patients.

Primary biliary cirrhosis in Singapore: Evaluation of demography, prognostic factors and natural course in a multi‐ethnic population

Primary biliary cirrhosis (PBC) is infrequent in Asians. Among Asian patients with PBC, information on natural course is scarce. The aim of this study was to study the clinical course and prognosticators among Asians with PBC. During 1990-2005, patients diagnosed with PBC at the National University Hospital, Singapore, constituted the retrospective cohort. Their demographic characteristics were evaluated. To evaluate the prognostic factors and natural course, two outcome measures were assessed: hepatic decompensation and death or liver transplant. Multivariate analysis was undertaken to identify factors associated with hepatic decompensation and terminal event (death or liver transplantation). Thirty-four PBC patients aged 56.8 +/- 1.8 years (mean +/- SEM) of whom 32 (94%) were women were included. Thirty-two (94%) of them were of Chinese origin. At presentation, 18 (53%) were symptomatic in the form of jaundice (n = 9, 26.5%), pruritus (n = 6, 17.6%) and fatigue (n = 5, 14.7%). During 4.80 +/- 0.7 (range 0.02-15.03) years follow up, 6/16 (37.5%) asymptomatic patients developed symptoms. After 5 years, 17.6% (n = 6) and 8.8% (n = 3) had hepatic decompensation and terminal event, respectively. Sicca syndrome was present in 26% (n = 9) of patients. Multivariate analysis revealed that serum bilirubin level at presentation was the sole determinant of decompensation. Rate of change of laboratory indices did not predict either event. In Singapore, Chinese women constitute most of the PBC patients. Elevated serum bilirubin level at presentation was the sole predictive marker associated with dismal outcome.

Liver cirrhosis in HIV‐infected patients: prevalence, aetiology and clinical outcome

Liver disease is frequently seen in HIV+ patients as a result of coinfection with hepatitis B (HBV) or C (HCV) viruses, alcohol abuse and/or exposure to hepatotoxic drugs. The aim of this study was to assess the prevalence of liver cirrhosis, its main causes and clinical presentation in HIV+ patients. Observational, cross-sectional, retrospective study of all HIV+ individuals followed at one reference HIV outpatient clinic in Madrid. Liver fibrosis was measured in all cases using transient elastometry (FibroScan). All 2168 HIV+ patients on regular follow-up (76% males, 46% injecting drug users) were successfully examined by FibroScan) between October 2004 and August 2006. Liver cirrhosis was recognized in 181 (overall prevalence, 8.3%), and the main aetiologies were HCV, 82.3%; HBV, 1.6%; dual HBV/HCV, 2.8%; and triple HBV/HCV/ hepatitis delta virus (HDV) infection, 6.6%. The prevalence of cirrhosis differed among patients with distinct chronic viral hepatitis: HCV, 19.2%; HBV, 6.1%; HBV/HCV, 41.7%; and HBV/HCV/HDV, 66.7%. In 12 patients with cirrhosis (6.7%), no definite aetiology was recognized. Overall, cirrhotics had lower mean CD4 counts than noncirrhotics (408 vs 528 cells/microL respectively; P = 0.02), despite similar proportion of subjects with undetectable viraemia on highly active antiretroviral therapy. Clinical manifestations of liver cirrhosis were: splenomegaly, 61.5%; oesophageal varices, 59.8%; ascites, 22.6%; encephalopathy, 12.1%; and variceal bleeding, 6.1%. Liver cirrhosis and hepatic decompensation events are relatively frequent in HIV+ individuals. Chronic HCV and alcohol abuse, but not chronic HBV, play a major role. Transient elastometry may allow the identification of a significant number of HIV+ individuals with asymptomatic liver cirrhosis.

Long-term safety of lamivudine treatment in patients with chronic hepatitis B

Background & aims: Data on thelong-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10% of thelamivudine-treated patients in year 1 and in 18%–21% in years 2–5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23% in year 1 to 65% in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations ( P < 0.005). The occurrence of hepatic decompensation (0%–2%) and LDR SAEs (1%–10%) among patients with lamivudine resistance remained stable during the first 4 years with mutations and increased afterward to 6% ( P = 0.03) and 20% ( P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease.