Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel.
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Humans↗
Biomedical subjects
Thierry Poynard
Publications and source records attributed to Thierry Poynard.
Polymorphonuclear neutrophils are a source of hepatocyte growth factor in patients with severe alcoholic hepatitis.
BACKGROUND/AIMS: Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in liver regeneration. Plasma HGF levels correlate with survival and hepatocyte proliferation in alcoholic hepatitis (AH). As AH is accompanied by inflammation, neutrophilia and polymorphonuclear neutrophil (PMN) infiltration of the liver, we postulated that PMN could be a source of HGF in such patients. METHODS: We studied 25 patients with severe AH in comparison with 20 alcoholic cirrhotic patients without AH and 20 healthy controls; the impact of a 28-day course of corticosteroids was evaluated in patients with AH. RESULTS: On day 0, HGF plasma and homogenized liver tissue levels were markedly increased in AH patients as compared to controls. The role of PMN in HGF production during AH was confirmed by a significantly higher ex-vivo HGF production capacity of lipopolysaccharide-stimulated blood PMN from AH patients relative to both control groups. Formyl-Methionyl-Leucyl-Phenylalanine-induced PMN release of HGF (degranulation conditions) was also higher in AH patients. In this setting, we found that HGF release by PMN ex vivo correlated strongly with HGF plasma levels, and that the degree of hepatic PMN correlated strongly with hepatic HGF levels. HGF plasma levels and ex-vivo HGF release by PMN were unaffected by steroid therapy. CONCLUSIONS: These findings suggest that, by releasing HGF, PMN could participate in liver regeneration during severe alcoholic hepatitis.
Adrenal Cortex Hormones↗
Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH.
BACKGROUND/AIMS: Controversy surrounding the efficacy of corticosteroids in severe alcoholic hepatitis (AH) persists. THE AIMS OF OUR STUDY WERE: (a) to analyze individual data of patients with severe AH discriminant function (DF)> or =32 from the last three randomized controlled trials; and (b) to identify the independent prognostic factors associated with short-term survival. METHODS: Individual data were collected from the three principal investigators. Survival analysis was performed at 28 days using the Kaplan-Meier method and log-rank test. The independent prognostic values were assessed by the proportional hazards regression model. RESULTS: About 102 placebo and 113 corticosteroid patients with DF > or =32 were analyzed. At 28 days, corticosteroid patients had significantly higher survival: 84.6+/-3.4% vs. 65.1+/-4.8%, P=0.001. In univariate analysis, corticosteroid treatment, age, DF, albumin, creatinine and encephalopathy were prognostic factors. In multivariate analysis, age (P=0.0001), serum creatinine (P<0.002) and corticosteroid treatment (P=0.002) were independent prognostic variables. A more dramatic decrease of median serum bilirubin values (micromol/l) was observed at 7 and 14 days in corticosteroid patients (P<0.05) : -76.5 vs. -35 and -105 vs. -45. CONCLUSIONS: Corticosteroids improved short-term survival of patients with severe AH. Age and serum creatinine are independent prognostic factors. Corticosteroids are recommended for patients with severe AH.
Adrenal Cortex Hormones↗
Impact of treatment on extra hepatic manifestations in patients with chronic hepatitis C.
BACKGROUND/AIMS: Fatigue and other extra hepatic manifestations of hepatitis C have never been studied prospectively in a large cohort. The aim was to assess the prevalence of these symptoms prior to any treatment, and on prolonged follow-up in treated and untreated patients. METHODS: A single-center cohort of consecutive patients with chronic hepatitis C was investigated prior to any treatment. A questionnaire was completed every 6 months for 18 months of follow-up. RESULTS: Of 1614 patients, 431 met the inclusion criteria (56% male; age 49 years; 60% with significant fibrosis or cirrhosis; 46% with cryoglobulinemia). Seventy-six were untreated; of the treated patients, 83 were sustained responders, 47 relapsers and 225 non-responders. At baseline, fatigue and other extrahepatic manifestations were present in 254 (59%) and 225 (52%) patients. Fatigue was improved in 29 of 83 (35%) responders versus 75 of 348 (22%) patients with detectable hepatitis C virus (HCV)-RNA (P=0.01). The impact of virologic response on fatigue persisted after adjusting for age, gender, fibrosis stage, and depression (odds ratio: 0.34, P<0.001). A cryoglobulin was detectable in two of 34 (6%) responders versus 38 of 115 (33%) patients with detectable HCV-RNA (P<0.001). CONCLUSIONS: In hepatitis C, a sustained virologic response is associated with a reduction in fatigue and cryoglobulin, but fatigue frequently persists despite a virologic response.
Adult↗
Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study.
BACKGROUND & AIMS: Type 1 hepatorenal syndrome (HRS) is a severe complication of cirrhosis associated with a short median survival time (<2 weeks). Although the administration of terlipressin improves renal function, its effect on survival is unknown. This study investigated predictive factors of survival in patients with type 1 HRS treated with terlipressin. METHODS: Ninety-nine patients with type 1 HRS treated with terlipressin in 24 centers were retrospectively studied. Terlipressin-induced improved renal function was defined as a decrease in serum creatinine value to <130 micromol/L or a decrease of at least 20% at the end of treatment. RESULTS: At inclusion, the Child-Pugh score was 11.8 +/- 1.6 (mean +/- SD). Terlipressin (3.2 +/- 1.3 mg/day) was administered for 11 +/- 12 days. Renal function improved in 58% of patients (serum creatinine decreased by 46% +/- 17% from 272 +/- 114 micromol/L). Median survival time was 21 days. Survival rate was 40% at 1 month. Multivariate analysis showed that improved renal function and Child-Pugh score < or =11 at inclusion were independent predictive factors of survival (P < 0.0001 and 0.02, respectively). Thirteen patients underwent liver transplantation (92 +/- 95 days after HRS onset), 10 of whom had received terlipressin and had had improved renal function. CONCLUSIONS: This retrospective uncontrolled study shows that in patients with type 1 HRS, terlipressin-induced improved renal function is associated with an increase in survival. Thus, a randomized trial investigating the effect of terlipressin on survival in patients with type 1 HRS should be performed.
Aged↗
Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C.
BACKGROUND & AIMS: Liver fibrosis is an important prognostic factor in patients with hepatitis C. The effect of pegylated (PEG) interferon alone or its combination with ribavirin on fibrosis has not been established. METHODS: We pooled individual data from 3010 naive patients with pretreatment and posttreatment biopsies from 4 randomized trials. Ten different regimens combining standard interferon, PEG interferon, and ribavirin were compared. The impact of each regimen was estimated by the percentage of patients with at least 1 grade improvement in the necrosis and inflammation (METAVIR score), the percentage of patients with at least 1 stage worsening in fibrosis METAVIR score, and by the fibrosis progression rate per year. RESULTS: Necrosis and inflammation improvement ranged from 39% (interferon 24 weeks) to 73% (optimized PEG 1.5 and ribavirin; P < 0.001). Fibrosis worsening ranges from 23% (interferon 24 weeks) to 8% (optimized PEG 1.5 and ribavirin; P < 0.001). All regimens significantly reduced the fibrosis progression rates in comparison to rates before treatment. The reversal of cirrhosis was observed in 75 patients (49%) of 153 patients with baseline cirrhosis. Six factors were independently associated with the absence of significant fibrosis after treatment: baseline fibrosis stage (odds ratio [OR] = 0.12; P < 0.0001), sustained viral response (OR = 0.36; P < 0.0001), age < 40 years (OR = 0.51; P < 0.001), body mass index < 27 kg/m(2) (OR = 0.65; P < 0.001), no or minimal baseline activity (OR = 0.70; P = 0.02), and viral load < 3.5 millions copies per milliliter (OR = 0.79; P = 0.03). CONCLUSIONS: PEG-interferon and ribavirin combination significantly reduces the rate of fibrosis progression in patients with hepatitis C.
Adult↗
Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C.
BACKGROUND & AIMS: Patient adherence to prescribed antiviral therapy in human immunodeficiency virus infection enhances response. We evaluated the impact of adherence to combination therapy with interferon or peginterferon plus ribavirin in chronic hepatitis C patients. METHODS: We assessed the effect of dose reduction on sustained virologic response (SVR) from prior trials with interferon alpha-2b plus ribavirin (n = 1010) or peginterferon alpha-2b 1.5 microg/kg/week plus ribavirin (n = 511). The actual treatment administered was verified from drug dispensing/return records and patient diaries. Two groups were defined: (1) patients who received >or=80% of both their total interferon and ribavirin doses for >or=80% of the expected duration of therapy and (2) patients who received reduced doses (<80% of one or both drugs for >or=80% of the expected duration of therapy). A statistical model provided comparative estimates of the response rates in compliant patients. RESULTS: Most patients were at least 80% compliant with interferon alpha-2b/ribavirin or peginterferon alpha-2b/ribavirin therapy and had SVR rates of 52% and 63%, respectively, for the 2 regimens. This was most apparent for HCV-1-infected patients. The impacts of adherence on efficacy from subgroup analysis and the statistical modeling approach were similar. CONCLUSIONS: HCV-1-infected patients who can be maintained on >80% of their interferon or peginterferon alpha-2b and ribavirin dosage for the duration of treatment in the setting of a clinical trial exhibit enhanced sustained response rates. Our results suggest that adherence will enhance the likelihood of achieving an initial virologic response. Adherence beyond 12-24 weeks will be advantageous only for those patients who have achieved such an early virologic response.
Adult↗
Long-term impact of renal transplantation on liver fibrosis during hepatitis C virus infection.
BACKGROUND & AIMS: During hepatitis C virus (HCV) infection, liver fibrosis progression after renal transplantation remains controversial. The aim of this cohort study with controls was to compare liver histopathologic features during HCV infection between renal transplant recipients and matched groups of hemodialyzed patients or controls without renal disease and untreated for HCV. METHODS: Each renal transplant recipient (group 1, n = 30) was matched at first liver biopsy (LB) using the main factors known to influence progression of fibrosis with one HCV hemodialyzed patient (group 2, n = 30) and one HCV-infected patient (nonhemodialyzed, nontransplanted; group 3, n = 30). Patients from group 1 were also matched with those of group 3 on the time between 2 consecutive LBs performed 37 months apart. LBs were evaluated according to the Knodell index, METAVIR score, and rate of fibrosis progression per year (fibrosis unit). RESULTS: The rate of fibrosis progression per year between the first and second LBs was significantly lower (P = 0.03) in group 1 (0.067; 95% confidence interval: -0.05, 0.18) than group 3 (0.20; 95% confidence interval: 0.13, 0.26). At the second LB, the Knodell index and activity or fibrosis in METAVIR were lower in group 1 than group 3 (4.2 +/- 0.4 vs. 7.5 +/- 0.6, 0.5 +/- 0.1 vs. 1.3 +/- 0.2, and 1.4 +/- 0.2 vs. 2.3 +/- 0.2 respectively, P < 0.01). CONCLUSIONS: Our study suggests that liver fibrosis progression is low in most HCV-infected renal transplant recipients with moderate liver disease at baseline.
Adult↗
Discussion on celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure.
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Celiac Disease↗
Portal lymphocytic infiltrate in alcoholic liver disease.
The aim of this study was to estimate the frequency of lymphocytic portal infiltrate in human alcoholic liver disease and to determine whether it was correlated with liver injury. This retrospective study included 200 consecutive patients referred between February 1996 and March 2001 to the Service Central d'Hépato-Gastroentérologie at Groupe Hospitalier Pitié-Salpêtrière Hospital, Paris, France. The inclusions criteria were as follows: (1) daily alcohol consumption greater than 40 g; (2) appropriate serological exclusion of B and C viral hepatitis; and (3) available liver biopsy specimen. Autoimmune hepatitis was excluded in all patients with the aid of a consensus scoring system. Forty percent of the patients had a predominantly lymphocytic portal infiltrate. On stepwise logistic regression of the predictive value of the 5 variables (gender, age, daily alcohol consumption, steatosis, and portal and septal fibrosis index), only 2 statistically independent predictors of predominant lymphocytic portal infiltrate were identified: portal and septal fibrosis index (P <.05) and age (P <.05). In conclusion, predominantly portal lymphocytic infiltrate occurs frequently in alcoholic liver disease, even in patients without serological markers of B and C viral hepatitis. Moreover, after adjustment for age, portal and septal fibrosis index remains significantly associated with the presence of a predominantly lymphocytic portal infiltrate. These results suggest that lymphocytes may play a role in the pathogenesis of alcohol-induced liver fibrosis.
Aged↗
Hepatic HCV RNA before and after treatment with interferon alone or combined with ribavirin.
The clinical use of measuring hepatic hepatitis C virus (HCV) RNA before and after therapy in patients with chronic hepatitis C has been assessed in a number of small clinical trials. Viral clearance from the liver may be a better marker of long-term response than eradication of serum HCV RNA. The aim of this study was to evaluate quantitative hepatic HCV-RNA measurements before and after antiviral therapy. Two thousand eighty-nine chronic hepatitis C patients were enrolled in 3 published clinical trials evaluating interferon alfa-2b alone or with ribavirin either as initial therapy or for interferon relapse. Hepatic HCV-RNA quantitation was performed with a modified reverse-transcription polymerase chain reaction (RT-PCR) before and 24 weeks after therapy in 951 and 1,316 patients, respectively. Pretherapy hepatic HCV-RNA concentrations correlated best with serum HCV-RNA concentrations (R =.236, P =.0001) and negatively correlated with alanine transaminase (ALT) values (-0.178, P =.0001), duration of infection (-0.09, P =.02), parenchymal injury (-0.135, P =.0001), histologic activity index (HAI) inflammatory score (-0.085, P =.01), Knodell fibrosis score (-0.072, P =.03), and body weight (-0.078, P =.02). In paired liver biopsy specimens (n = 534), change in hepatic HCV RNA correlated with the change in the HAI (R =.346, P =.0001). Of 400 sustained virologic responders (SVR), 393 (98%) had undetectable hepatic HCV RNA, whereas 7 (2%) had detectable hepatic HCV RNA; 5 have been followed and 2 have had reappearance of serum HCV RNA 12 months after therapy. In conclusion, measurement of hepatic HCV RNA before or after therapy reflects changes observed in serum HCV RNA, and correlates inversely with hepatic inflammation and fibrosis, but otherwise has minimal clinical use.
Antiviral Agents↗
Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis.
Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with cryptogenic cirrhosis (CC-O), 10 lean patients with cryptogenic cirrhosis (CC-L) and 391 patients with hepatitis C virus-related cirrhosis (C-HCV). In CC-O patients, cirrhosis was detected later in life than in C-HCV and CC-L patients. Severe liver disease was as frequent in CC-O as in C-HCV patients as indicated by the proportion of Child B or C or of episodes of hepatic decompensation. Survival of CC-O patients was lower than that of untreated, age- and sex-matched C-HCV controls (P <.02 at 30 months), with a higher mortality of Child B or C patients. Hepatocellular carcinoma was detected in 8 of 27 (27%) CC-O patients versus 21% of matched C-HCV controls with a similar age cumulated incidence, suggesting a comparable carcinogenic potential. In conclusion, obesity-related cirrhosis should now be recognized as a distinct entity that can cause severe liver disease and death. Increased awareness of and better diagnostic strategies for nonalcoholic steatohepatitis in overweight patients are urgently needed.
Adult↗
NNRTI-related or -unrelated hepatotoxicity?
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Chemical and Drug Induced Liver Injury↗
Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study.
The aim of this retrospective study was to determine the predictive value of alanine aminotransferase (ALT) levels for histologic findings in patients with chronic hepatitis C virus (HCV) infection. Data on 864 HCV RNA-positive patients were collected. ALT values were obtained at the time of biopsy (before treatment), and normal ALT values were defined as normal values obtained at serial evaluations during a 6-month period. Histologic results were scored using the METAVIR system. Among all patients, 99% of those with elevated ALT levels had a score of at least F1 (positive predictive value [PPV], 99%) and 88% had a score greater than A1F1. Among patients with persistently normal ALT values, 65% had a score of at least F1 (negative predictive value [NPV], 35%) and 26% had a score greater than A1F1. The receiver operating characteristics analysis indicates that the ALT threshold for the best compromise sensitivity-specificity was about 2.25 times the upper limit of normal (ULN). In conclusion, almost all HCV RNA-positive patients with elevated ALT levels have some degree of fibrosis. However, an important proportion of patients with persistently normal ALT levels also show some histologic signs of fibrosis; the degree of fibrosis is usually mild but is sometimes more marked, and in rare cases cirrhosis may be present. In this subset of patients, the indication of liver biopsy and the potential benefit of therapy need to be further evaluated. These results suggest the need to revisit the algorithm for liver biopsy practice.
Alanine Transaminase↗
Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study.
OBJECTIVES: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin has been studied in several reports, two prospective pilot studies and a double-blind, short-term, controlled haemodynamic study. Promising results have been shown with this drug. The purpose of this multicentre retrospective study was to evaluate the effects of terlipressin on renal function and survival of patients with HRS. PATIENTS AND METHODS: Eighteen patients recruited in three liver units with type 1 HRS in 16 cases and type 2 HRS in two cases were given 4 mg/day terlipressin (range 1.5-12) for 7 days (range 2-16). Electrolytes, renal function, mean urinary output, natriuresis, liver function tests, and tolerance of the treatment were monitored regularly. RESULTS: A total of 13/18 (72%) patients responded with a mean decline in serum creatinine ranging from 31 to 75% from day 0 to day 5. Eight of these 13 patients had a normal serum creatinine level at day 5. Liver function tests remained unaffected by terlipressin administration. Three local necrosis complications were noted in patients receiving terlipressin continuously via an infusion pump. Two responder patients survived: one of these underwent orthotopic liver transplantation with a follow-up of 24 months; the other is alive with a follow-up of more than 36 months. Patients who responded to terlipressin had lower baseline serum bilirubin and significantly higher serum sodium concentrations than patients who did not respond. CONCLUSION: In this pilot study, improvement in renal function was noted in 72% of cases after administration of terlipressin, and was associated with long-term survival in two patients. Parameters associated with response to terlipressin and increased survival should be defined better in a large cohort of cirrhotic patients with HRS.
Aged↗
Biochemical markers of liver fibrosis: a comparison with historical features in patients with chronic hepatitis C.
OBJECTIVES: Liver fibrosis in chronic hepatitis C is related to sex, age at infection, duration of infection, and alcohol consumption. Several noninvasive biochemical markers are highly predictive for the discrimination of significant fibrosis. The aims of this study were: 1) to compare an index of five biochemical markers with historical features; and 2) to determine the utility of combining these features with the five-marker index for the prediction of significant fibrosis. METHODS: Untreated patients with chronic hepatitis C and a known duration of infection had a liver biopsy and serum tested for markers of fibrosis. The discriminative values of the markers and an index of historical features for the diagnosis of clinically significant fibrosis (F2-F4 by the Metavir system) were compared using areas under receiver operating characteristic (ROC) curves. A modified index was constructed combining the five-marker index and historical features. RESULTS: A total of 211 patients were included. Of these, 52% were male, and 19% consumed > or = 50 g of alcohol daily. The median age at infection was 28 +/- 13 yr and the median duration of infection was 17 +/- 8 yr (range 1-48 yr). By multivariate logistic regression analysis, sex (p = 0.003), age at biopsy (p = 0.004), and alcohol consumption (p = 0.042) were independently predictive of F2-F4 fibrosis. For the discrimination of F2-F4 fibrosis, the areas under the ROC curves were 0.796 +/- 0.033 for the five-marker index versus 0.709 +/- 0.037 for the historical index (p = 0.079). For diagnosis of advanced fibrosis (F3 and F4), the areas under the curves were 0.920 +/- 0.032 and 0.762 +/- 0.049 (p = 0.007), respectively. The discriminative value of the combined biochemical and historical index was not statistically significantly different from that of the five-marker index alone (p = ns). CONCLUSIONS: A simple index including age, sex, and five biochemical markers accurately predicts significant hepatitis C-related fibrosis. This index is more accurate than an index of historical features, the addition of which to the existing index was not helpful.
Adult↗
[What are the indications for treatment of acute hepatitis C?].
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Acute Disease↗