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1.
J Viral Hepat ; 25(8): 920-929, 2018 08.
Article in English | MEDLINE | ID: mdl-29532619

ABSTRACT

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi-centre cohort of HBV-HCV subjects, and by performing a systematic review and meta-analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV-HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV-HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV-HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV-HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV-HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV-HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53-1.6) although there was significant heterogeneity (I2 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV-HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV-induced steatogenesis by HBV in certain subgroups of patients.


Subject(s)
Coinfection/complications , Fatty Liver/epidemiology , Fatty Liver/pathology , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Adult , Female , Humans , Male , Middle Aged , Prevalence , Retrospective Studies
2.
J Viral Hepat ; 25(2): 152-160, 2018 02.
Article in English | MEDLINE | ID: mdl-29159841

ABSTRACT

In order to accurately assess the burden of hepatitis C (HCV) and develop effective interventions, we must understand the magnitude and trends of mortality related to the disease. In the United States, HCV-related mortality is continuously increasing. We have no comparable data for Switzerland and other European countries, although a modelling study predicted a similar increase. We analysed time trends (1 January 1995-31 December 2014) in HCV-specific mortality rates in the Swiss general population using the death registry of the Swiss Federal Statistical Office (SFSO). We compared HCV-related mortality to HIV-related and hepatitis B (HBV)-related mortality. To determine potential under-reporting in HCV-related mortality, we probabilistically linked the SFSO data to persons who died in the Swiss Hepatitis C Cohort Study (SCCS). SFSO data showed that HCV-related mortality more than doubled between 1995 and 2003, but has since stabilized at ~2.5/100 000 person-years. Since 2000, HCV-related mortality has been higher than HIV-related mortality and was about fivefold higher in 2014. HBV-related mortality remained low at ~0.5/100 000 person-years. Of 4556 persons in the SCCS, 421 have died and 86.2% could be linked to the death registry. According to the SCCS, 133 deaths were HCV-related. HCV was not mentioned on the SFSO death certificate of 45% of these (n = 60/133). In conclusion, HCV-related mortality remained constant, possibly because quality of care was high, or because of under-reporting or because mortality has not yet increased. However, HCV-related mortality is now much higher than HIV- and HBV-related mortality, and under-reporting was common.


Subject(s)
Hepatitis C, Chronic/mortality , Hepatitis C/mortality , Registries , Adult , Cohort Studies , Female , HIV Infections/mortality , Humans , Male , Middle Aged , Switzerland/epidemiology , United States/epidemiology
3.
J Viral Hepat ; 23(9): 697-707, 2016 09.
Article in English | MEDLINE | ID: mdl-27006320

ABSTRACT

Socio-demographic and behavioural characteristics are associated with delayed diagnosis and disease progression in HCV-infected persons. However, many analyses focused on single variables rather than groups defined by several variables. We used latent class analysis to study all 4488 persons enrolled in the Swiss Hepatitis C Cohort Study. Groups were identified using predefined variables at enrolment. The number of groups was selected using the Bayesian information criterion. Mortality, loss to follow-up, cirrhosis, treatment status and response to antivirals were analysed using Laplace and logistic regressions. We identified five groups and named them according to their characteristics: persons who inject drugs, male drinkers, Swiss employees, foreign employees and retirees. Two groups did not conform to common assumptions about persons with chronic hepatitis C and were already in an advanced stage of the disease at enrolment: 'male drinkers' and 'retirees' had a high proportion of cirrhosis at enrolment (15% and 16% vs <10.3%), and the shortest time to death (adjusted median time 8.7 years and 8.8 years vs >9.0). 'Male drinkers' also had high substance use, but they were well educated and were likely to be employed. This analysis may help identifying high-risk groups which may benefit from targeted interventions.


Subject(s)
Antiviral Agents/therapeutic use , Health Services Accessibility , Hepatitis C, Chronic/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Switzerland , Treatment Outcome , Young Adult
5.
Aliment Pharmacol Ther ; 42(11-12): 1250-60, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26472616

ABSTRACT

BACKGROUND: The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients. AIM: To synthesise the available evidence on the efficacy of self-expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. METHODS: Meta-analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. RESULTS: Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31-0.49) for death, 0.41 (95% CI = 0.29-0.53) for liver-related death and 0.36 (95% CI = 0.26-0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07-0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11-0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04-0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17-0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04-0.21) and 0.26 (95% CI = 0.18-0.36), respectively]. CONCLUSIONS: Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.


Subject(s)
Esophageal and Gastric Varices/therapy , Liver Cirrhosis/therapy , Self Expandable Metallic Stents , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Humans , Liver Transplantation/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic , Prognosis , Risk Factors
6.
Gut ; 64(10): 1605-15, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25214320

ABSTRACT

OBJECTIVE: The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN: We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥ 0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥ 20 g/day for ≥ 5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS: Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS: Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.


Subject(s)
Hepacivirus/genetics , Hepatitis C, Chronic/complications , Liver Cirrhosis/etiology , Polymorphism, Single Nucleotide , RNA, Viral/analysis , Risk Assessment/methods , Biopsy , Disease Progression , Female , Genome-Wide Association Study , Hepatitis C, Chronic/virology , Humans , Incidence , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Male , Retrospective Studies , Risk Factors , Switzerland/epidemiology , Time Factors
7.
Am J Transplant ; 14(10): 2206-20, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25091274

ABSTRACT

Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.


Subject(s)
Hepatitis C, Chronic/surgery , Kidney Transplantation , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Humans , Kidney Transplantation/adverse effects
11.
Rev Med Suisse ; 9(396): 1594, 1596-8, 2013 Sep 04.
Article in French | MEDLINE | ID: mdl-24066468

ABSTRACT

The hepatitis E virus (HEV) is an RNA virus transmitted via the fecal-oral route or through uncooked animal meat products. Of the 4 known genotypes, genotype 3 is responsible for autochthonous infections in industrialized countries, with a seroprevalence in Switzerland estimated as high as 22%. The majority of infections is asymptomatic but a minority of patients, notably men over 50 or with underlying liver disease, can present with severe acute hepatitis. Chronic hepatitis E with HEV of genotype 3 has been observed in immunosuppressed patients, mostly transplant recipients. Serology is not sufficiently sensitive, especially in immunosuppressed patients, making PCR identification the preferred test for diagnosing active infection. Ribavirin or interferon-alpha can be used to treat chronic hepatitis E if reduction of immunosuppressive treatment does not result in viral elimination.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis E virus/isolation & purification , Hepatitis E/therapy , Immunocompromised Host , Adolescent , Adult , Age Factors , Female , Genotype , Hepatitis E/epidemiology , Hepatitis E/virology , Hepatitis E virus/genetics , Humans , Male , Middle Aged , Risk Factors , Seroepidemiologic Studies , Sex Factors , Switzerland/epidemiology , Young Adult
13.
Rev Med Suisse ; 8(352): 1665-8, 2012 Sep 05.
Article in French | MEDLINE | ID: mdl-22988726

ABSTRACT

Portal hypertension is regularly encountered by the general practitioner. It is defined by an elevation of the porto-systemic pressure gradient, with complications such as ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, hypersplenism, hepatopulmonary syndrome or hepatic encephalopathy occuring when a significant elevation of this gradient is reached. Cirrhosis is the primary cause of portal hypertension in industrialized countries. Symptomatic portal hypertension carries a poor prognosis. Management should be initiated rapidly, including the identification and correction of any reversible underlying condition. Liver transplantation should be considered in advanced cases.


Subject(s)
Ascites/therapy , Hypertension, Portal/complications , Ascites/classification , Ascites/etiology , Diuretics/therapeutic use , Humans , Mineralocorticoid Receptor Antagonists/therapeutic use , Paracentesis , Severity of Illness Index
14.
Rev Med Suisse ; 8(352): 1669-70, 1672-3, 2012 Sep 05.
Article in French | MEDLINE | ID: mdl-22988727

ABSTRACT

Fecal calprotectin (FC) is a valid biomarker to discriminate with a good sensitivity and specificity the presence of mucosal lesions of the gastrointestinal tube (e.g. ulcers in the context of inflammatory bowel disease (IBD)) from functional disorders (e.g. irritable bowel syndrome). FC is not specific for IBD and can be elevated also in gastrointestinal infections, ischemic colitis or neoplasia. An elevated FC should stimulate further investigations, notably an endoscopic workup. The level of FC correlates with the endoscopic score in Crohn's disease and ulcerative colitis. The correlation of FC and the endoscopic severity is better than the one of CRP or blood leukocytes. Thus, FC can also be used in the follow-up of IBD patients.


Subject(s)
Feces/chemistry , Inflammatory Bowel Diseases/diagnosis , Leukocyte L1 Antigen Complex/analysis , Biomarkers/analysis , Humans
15.
J Viral Hepat ; 19(8): 568-73, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22762141

ABSTRACT

Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies.


Subject(s)
Autoantibodies/immunology , Cytochrome P-450 CYP2D6/metabolism , Hepatitis C, Chronic/pathology , Adult , Aged , Cohort Studies , Cytochrome P-450 CYP2D6/genetics , Dextromethorphan/metabolism , Dextrorphan/metabolism , Female , Genotype , Humans , Male , Middle Aged , Switzerland
16.
J Viral Hepat ; 18(5): 305-15, 2011 May.
Article in English | MEDLINE | ID: mdl-21470343

ABSTRACT

Hepatitis C virus (HCV) nonstructural protein 3-4A (NS3-4A) is a complex composed of NS3 and its cofactor NS4A. It harbours serine protease as well as NTPase/RNA helicase activities and is essential for viral polyprotein processing, RNA replication and virion formation. Specific inhibitors of the NS3-4A protease significantly improve sustained virological response rates in patients with chronic hepatitis C when combined with pegylated interferon-α and ribavirin. The NS3-4A protease can also target selected cellular proteins, thereby blocking innate immune pathways and modulating growth factor signalling. Hence, NS3-4A is not only an essential component of the viral replication complex and prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. This review provides a concise update on the biochemical and structural aspects of NS3-4A, its role in the pathogenesis of chronic hepatitis C and the clinical development of NS3-4A protease inhibitors.


Subject(s)
Carrier Proteins/metabolism , Hepacivirus/metabolism , Hepatitis C, Chronic/virology , Viral Nonstructural Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Vesicular Transport/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/chemistry , Carrier Proteins/genetics , Drug Resistance, Viral/genetics , Hepacivirus/enzymology , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Humans , Intracellular Signaling Peptides and Proteins , Mitochondrial Proteins/antagonists & inhibitors , Mitochondrial Proteins/chemistry , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Mutation , Nucleoside-Triphosphatase/antagonists & inhibitors , Nucleoside-Triphosphatase/chemistry , Nucleoside-Triphosphatase/genetics , Nucleoside-Triphosphatase/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 2/metabolism , RNA Helicases/antagonists & inhibitors , RNA Helicases/chemistry , RNA Helicases/genetics , RNA Helicases/metabolism , Serine Proteases/chemistry , Serine Proteases/genetics , Serine Proteases/metabolism , Serine Proteinase Inhibitors/pharmacology , Serine Proteinase Inhibitors/therapeutic use , Signal Transduction , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , Virus Replication
18.
Rev Med Suisse ; 7(277): 25-9, 2011 Jan 12.
Article in French | MEDLINE | ID: mdl-21309170

ABSTRACT

This review highlights recent advances in gastroenterology and hepatology, including the treatment of Crohn's disease, of eosinophilic esophagitis, of chronic hepatitis C, and of hepatic encephalopathy as well as the role of high resolution manometry in the investigation of esophageal motility disorders. These new developments will be summarized and discussed critically, with a particular emphasis on their potential implications for current and future clinical practice.


Subject(s)
Digestive System Diseases/therapy , Antiviral Agents/therapeutic use , Gastrointestinal Agents/therapeutic use , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Manometry , Vitamin E/therapeutic use , Vitamins/therapeutic use
20.
Rev Med Suisse ; 6(233): 168-70, 172-3, 2010 Jan 27.
Article in French | MEDLINE | ID: mdl-20214187

ABSTRACT

Chronic hepatitis B predisposes to the development of cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis B is aimed at halting viral replication and, thereby, hepatic inflammation. Treatment indication should be established carefully and with full knowledge of the advantages and limitations of currently available antiviral drugs. Patients on long-term nudcleos(t)ide analogue treatment should be followed regularly in order to avoid the appearance of antiviral resistance. The purpose of this review is to provide a concise overview of the diagnosis and management of chronic hepatitis B.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Drug Resistance, Viral , Genotype , Hepatitis B, Chronic/genetics , Hepatitis B, Chronic/virology , Humans
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