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Z M Younossi

Publications and source records attributed to Z M Younossi.

At least 19 recordsLinked to original sources
PubMed2006

Non-alcoholic fatty liver disease and hepatitis C infection.

Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.

Fatty Liver↗
PubMed2006

The metabolic syndrome and nonalcoholic fatty liver disease.

Accumulating evidence supports an association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome, diabetes, and obesity. The epidemiology, pathogenesis, and approach to treatment of NAFLD follow the same trends as these other metabolic disorders, and insulin resistance is the key event linking NAFLD to these diseases. The impairment in fat and glucose metabolism that ensues once insulin resistance occurs leads to similar biochemical and clinical abnormalities in patients with NAFLD. Many recent studies investigating the cellular and genetic basis of these diseases have led to a better understanding of their pathogenesis and insight into treatment and management. The most effective treatment thus far is weight loss and the use of insulin-modulating pharmacologic agents. A few additional treatment strategies include the use of lipid-lowering, antioxidants or cytoprotective agents, but there is no single therapeutic approach that is effective for managing NAFLD. Future therapies may combine drugs that target specific pathways involved in NAFLD pathogenesis.

Diabetes Mellitus, Type 2↗
PubMed2003

Survival and resource utilization in liver transplant recipients: the impact of admission to the intensive care unit.

The organ allocation system for liver transplantation was recently changed to address criticisms that it was too subjective and relied too heavily on total waiting time. The new system, Model for End-Stage Liver Disease and Pediatric Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the risk of 3-month pretransplant mortality, allocating livers thereby. There is concern that such a scheme gives priority to the sickest patients, who may not enjoy good posttransplant outcomes. The aim of the present study was to compare the outcomes of liver transplant recipients who had been admitted to the intensive care unit (ICU) to those who had not. Admission to the ICU is considered here to be another indicator of the severity of illness. Patients who underwent liver transplantation at the Cleveland Clinic between January 1, 1993 and October 31, 1998 and were at least 18 years of age were coded for liver transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three groups: those who had been admitted to an ICU before transplantation (group A, n = 16), those who had been admitted to the hospital but not to an ICU (group B, n = 63), and those who were living at home and had undergone an elective transplant (group C, n = 33). Clinical and demographic information (age, sex, race, disease severity, disease etiology, and cold ischemia time) were associated with patient survival, patient/graft survival, and posttransplant resource utilization (hospital length of stay and hospital charges). Age, sex, race, etiology of disease, and cold ischemia time were similar among the three groups. Patient survival, patient/graft survival, and hospital charges were not statistically different between the three groups. The median length of stay was statistically different only between groups B and C (P =.006). Our data support the idea that if severely ill patients with end-stage liver disease are selected appropriately, liver transplant outcomes are similar to those observed among subjects who are less ill and are transplanted electively from home.

Female↗
PubMed2001

Cost effectiveness of screening for hepatitis C virus in asymptomatic, average-risk adults.

PURPOSE: To estimate the cost effectiveness of screening for hepatitis C in asymptomatic, average-risk adults. METHODS: We used a Markov decision analysis model to estimate the lifetime cost effectiveness of three screening strategies: (1) initial screening for hepatitis C antibody by third-generation enzyme-linked immunosorbent assay (ELISA), followed by confirmatory testing for hepatitis C virus ribonucleic acid (RNA) using polymerase chain reaction (PCR); (2) initial screening for hepatitis C virus RNA by PCR only; and (3) the current practice of not screening. The patient population comprised a hypothetical cohort of average-risk adults presenting to their regular primary health care provider for routine physical examination. The main outcome measure was cost per additional quality-adjusted life-year (QALY) gained. RESULTS: The no screening strategy was the dominant strategy in the baseline analysis. The model was most sensitive to the reduction in quality of life related to patient awareness of hepatitis C infection. Screening with ELISA and PCR was preferred when this value was <0.01 and was cost effective if more than half of the patients who tested positive for hepatitis C actually initiated treatment, or if the annual rate of progression to cirrhosis was greater than 2.5%. Screening with PCR only was never cost effective. CONCLUSIONS: This analysis does not support the widespread screening for hepatitis C among asymptomatic, average-risk adults.

Adult↗
PubMed2001

Interferon alpha 2B and ribavirin in severe recurrent cholestatic hepatitis C.

Severe recurrent cholestatic hepatitis C after liver transplantation has a poor prognosis and no standard therapy is currently available. Four cases of severe recurrent cholestatic hepatitis C treated with a combination of interferon alpha 2b and ribavirin are described. All four patients were transplanted for hepatitis C-related cirrhosis. The mean age at transplantation was 45 years (range 41-51 years). Three of the patients were male and one was female. All four patients had hepatitis C virus viremia before and after liver transplantation. At 2 to 23 months after liver transplantation, all four patients developed jaundice, cholestatic elevation of liver enzymes, and histopathology consistent with severe recurrent cholestatic hepatitis C. Combination of interferon and ribavirin was given with prompt virological suppression. Despite this rapid viral suppression, all four patients developed progressive graft failure with three deaths.

Adult↗
PubMed2001

A randomized, double-blind controlled trial of interferon alpha-2b and ribavirin vs. interferon alpha-2b and amantadine for treatment of chronic hepatitis C non-responder to interferon monotherapy.

BACKGROUND/AIMS: Interferon-based regimens (alone or with ribavairin) are standard therapies for chronic hepatitis C. The aim of this study was to compare a 24-week regimen of interferon alpha-2b + ribavirin (IFN + RIBA) to interferon alpha-2b + amantadine (IFN + AMANT) in non-responders to previous interferon monotherapy. METHODS: In a multi-center, double-blind clinical trial, 118 patients (non-responders to previous interferon monotherapy) were equally randomized into the two arms: interferon alpha-2b (3 MU thrice weekly) and ribavirin (800 mg daily) vs. interferon alpha-2b (3 MU thrice weekly) and amantadine (200 mg daily). RESULTS: After 24 weeks of therapy, HCV RNA became undetectable in 34.8% (95% CI: 23.7-49.2) of IFN + RIBA and 19.6% (95% CI: 10.6-34.7) of IFN + AMANT (P = 0.10). This response was sustained in 3.9% (95% CI: 1.0-14.9) of IFN + RIBA and 0% of IFN + AMANT (P = 0.16). Ten patients from IFN + AMANT (17%) and 12 patients (20%) from IFN + RIBA were discontinued before completion of therapy. Of these, 7% in IFN + AMANT and 12% in IFN + RIBA were discontinued due to adverse effects. CONCLUSIONS: Re-treatment of interferon non-responders with a 24-week course of IFN + AMANT was not associated with any sustained viral eradication. Although IFN + RIBA in this group was associated with a reasonable end of treatment response, relapses were common and sustained responses were low.

Adult↗
PubMed2001

Chronic hepatitis C and superimposed nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Hepatitis C and nonalcoholic fatty liver disease (NAFL) are the two most common forms of liver disease in the United States. Recently, obesity and its associated risk factors have been suggested to enhance HCV-related fibrosis. The aim of this study was to assess the impact of hepatic steatosis, steatohepatitis, and its associated risk factors on HCV-related fibrosis. METHODS: Patients with untreated, biopsy-proven, chronic hepatitis C (6/97-3/99) were included. Clinical and demographic data at the time of liver biopsy were obtained from chart review and verified by telephone survey. One hepatopathologist reviewed all pathologic specimens, using the modified histological activity index score and the Ishak staging for fibrosis and a NAFL pathologic protocol. RESULTS: One hundred and seventy patients with hepatitis C were included [age: 48.7+/-9.33 (years), body mass index (BMI): 28.1+/-5.7 (kg/m2) and type 2 diabetes mellitus (DM): 14%]. Of these, 77 (45.3%) had no or mild fibrosis and 93 (54.7%) had advanced fibrosis. Hepatic steatosis was seen in 90 (52.9%) patients. The grade of steatosis was associated with markers of obesity only. Age (p=0.002), type 2 DM (p=0.04), and superimposed steatohepatitis (p=0.047) were independently associated with advanced fibrosis. Superimposed nonalcoholic steatohepatitis (NASH) was seen in 17 (10%) patients. Patients with superimposed NASH were mostly obese (76.5%), males (62%) with 16% having type 2 diabetes and a BMI 33.8+/-7.12. CONCLUSION: In patients with chronic hepatitis C, type 2 DM and superimposed steatohepatitis are independently associated with advanced fibrosis.

Adult↗
PubMed2001

Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease.

Some patients diagnosed with cryptogenic cirrhosis may have "burned-out" nonalcoholic fatty liver disease (NAFL). To test this hypothesis, we used our liver transplant database (November 1984 to November 1998) to assess the incidence of NAFL in patients with cryptogenic cirrhosis after orthotopic liver transplantation (OLT). We also examined the clinicodemographic features associated with post-OLT NAFL, obtained by chart review and telephone interviews. When available, post-OLT liver biopsy specimens were reviewed blindly by a hepatopathologist according to the NAFL pathology protocol. We identified 51 patients with cryptogenic cirrhosis (mean age, 51 +/- 12 years); 60% were women, 94% were white, and 34% had type 2 diabetes mellitus (DM). Mean pre-OLT body mass index (BMI) was 27.33 +/- 5.54 kg/m(2). Twenty-five patients underwent at least 1 post-OLT liver biopsy. Post-OLT NAFL was identified in 13 patients (25.4%), whereas post-OLT nonalcoholic steatohepatitis (NASH) was seen in 8 patients (15.7%). Features associated with post-OLT NASH were pre- and post-OLT type 2 DM (P < or =.05) and an elevated fasting triglyceride level (P <.05). BMI tended to be greater in patients with post-OLT NAFL or NASH. Those who did not develop post-OLT NAFL showed a decrease in BMI. Patients with cryptogenic cirrhosis undergoing OLT resemble patients with NAFL. Post-OLT NAFL and NASH can be seen in a number of patients with cryptogenic cirrhosis. This supports the notion that some cases of cryptogenic cirrhosis represent burned-out NAFL.

Adult↗
PubMed2001

Clinical features and natural history of nonalcoholic steatosis syndromes.

Nonalcoholic steatohepatitis, along with other forms of nonalcoholic fatty liver disease, is a chronic liver disease that is attracting increasing significance. It is a clinicopathologic syndrome that was originally described in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. This typical patient profile has been expanded and is now recognized to occur even in normal weight males without overt abnormalities in carbohydrate metabolism. Although originally believed to be a benign clinical entity, nonalcoholic steatohepatitis is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. It is important to emphasize that nonalcoholic steatohepatitis is best considered one type of a larger spectrum of nonalcoholic fatty liver disease that is a consequence of insulin resistance and ranges from fat alone to fat plus inflammation, fat plus ballooning degeneration, and nonalcoholic steatohepatitis, the latter being the most serious form. As with any disease, the clinical importance of nonalcoholic steatohepatitis is related to its prevalence and natural history. Recent studies using different methodologies indicate that in the general population the prevalence of fatty liver and nonalcoholic steatohepatitis is approximately 20% and 3%, respectively. These prevalence rates are increased in certain subpopulations such as obesity and type II diabetes. Of greater concern is the recognition that cirrhosis and liver-related deaths occur in approximately 20% and 8% of these patients, respectively, over a 10-year period. Risk factors for these adverse clinical symptoms include patients older than the age of 45, the presence of diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio > 1 and hepatic histology. However, a number of important unresolved issues must be clarified before the true natural history of this disease can be fully understood.

Chronic Disease↗
PubMed2001

Hepatitis C virus RNA assays: a comparison of SuperQuant and Monitor.

Hepatitis C RNA testing has been used extensively to assess the efficacy of antiviral therapy and has increasingly become an integral part of clinical management of patients with chronic hepatitis C. A variety of commercially available hepatitis C virus (HCV) RNA tests are used to detect HCV RNA qualitatively or quantitatively. These commercial tests have fundamental differences that are reflected on the values they generate. We compared two widely used assays, HCV SuperQuant (SQ) and Amplicor HCV Monitor (M1 and M2), in sera of patients with chronic hepatitis C. A total of 506 sera from 79 patients were tested with both assays. The data were logarithmically transformed and analyzed by linear regression and measurement of agreement. Two hundred thirty-eight sera had HCV RNA values within the dynamic range of both assays. The correlation between the assays was fair, with a correlation coefficient (r) of 0.699. Overall, SQ generated higher values than M1 with a mean difference of 0.558 log (SD = 0.624). One hundred ninety-four (38%) and 121 (24%) of the sera were below the dynamic range of M1 and SQ, respectively. Seventy-three sera, undetectable by M1, were positive by SQ. The Amplicor HCV Monitor 2.0 (M2) was performed in 66 sera. All were positive by SQ and M2, but only 38 were within the dynamic range of M1. The correlations between these tests were good (r = 0.68-0.78), but the agreement was rather poor. In conclusion, this study confirms that both SQ and M2 are more sensitive than M1. Additionally, our results show rather poor agreements between these assays. The recent attempts in standardizing the reporting of these assays should make their results more easily interchangeable.

Adult↗
PubMed2001

Assessment of utilities and health-related quality of life in patients with chronic liver disease.

OBJECTIVES: Quantitative measures of the value patients place on the state of their health is crucial to understanding their experience, and to calculate quality-adjusted years of life for economic analyses. Patients' values in chronic liver disease remain unexplored, although experts' estimates of utilities have been examined. Our study tests the validity of a widely used utility measure in chronic liver disease and, if valid, establishes the decrement in health-related quality associated with chronic liver disease. METHODS: A total of 120 patients with chronic liver disease participated in the study (age 50 +/- 10 yr; men 53%; cirrhosis 51%, chronic viral hepatitis 51%, and chronic cholestatic liver disease 30%). All patients completed three instruments: Health Utility Index Mark 2 (scores 0-1), Short Form-36 (scale scores 0-100), and a disease-specific health-related quality of life instrument (Chronic Liver Disease Questionnaire; scores 1-7). RESULTS: We found a moderate to strong correlation between scores on the three measures and that impairment worsened as the severity of disease worsened. Patients without cirrhosis and those with Child's A cirrhosis showed substantial decrement in utilities (0.82 and 0.83, respectively) in the range of patients surviving brain tumor. Those with Child's B and C showed a greater decrement (0.67 and 0.56) that was in the range experienced by patients who survive a stroke (0.67). Utilities assessed by Health Utility Index Mark 2 differed substantially from estimates by "expert." CONCLUSIONS: We conclude that utilities should be based on patient reports and that the data from this study can inform economic analyses in studies of patients with chronic liver disease.

Chronic Disease↗
PubMed2001

Health-related quality of life in chronic liver disease: the impact of type and severity of disease.

OBJECTIVE: The type and severity of chronic liver disease may have different effects on health-related quality of life (HRQL). The aim of our study was to determine whether HRQL in patients with chronic liver disease differs by type and severity of disease and to identify which clinical and physiological factors affect this impairment. METHODS: In this study, HRQL was measured with a generic (Short Form 36) and a liver disease-specific (Chronic Liver Disease Questionnaire) questionnaire. Clinical, demographic, and laboratory data were collected at office visits. Patient's HRQL scores were compared with the published norms and to the chronically ill populations. A total of 353 patients (mean age 50 yr, 51% men) with chronic liver disease, either viral disease (hepatitis B and C), cholestatic disease (primary biliary cirrhosis or primary sclerosing cholangitis), or hepatocellular disease were enrolled in the study. RESULTS: In general, HRQL in patients with chronic liver disease was lower than the normal population and was similar to that of patients with chronic obstructive pulmonary disease or congestive heart failure. In cirrhotic patients, some dimensions of HRQL were less impaired in patients with cholestatic disease than in those with hepatocellular diseases. More severe disease (higher Child's class) was associated with a lower Chronic Liver Disease Questionnaire score and the Short Form 36's physical component summary scores. Older age had a weak negative association with the physical aspects of HRQL. CONCLUSIONS: We conclude that chronic liver disease substantially reduces HRQL, and this impact does not differ markedly by type of disease. Older age and measures of disease severity were associated with poorer HRQL.

Age Factors↗
PubMed2001

Hepatitis C, cryoglobulinemia, and cutaneous vasculitis associated with unusual and serious manifestations.

Hepatitis C viral infection is currently the leading cause of chronic hepatitis and cirrhosis. It also is a major predisposing factor for the development of hepatocellular carcinoma. It is estimated that approximately 1-2% of patients with hepatitis C infection have nonhepatic manifestations that are protean in nature. In this report, we describe six unusual cases of nonhepatic manifestations: abdominal vasculitis in two, peripheral neuropathy in two, and one patient each with central nervous system vasculitis and necrotizing cutaneous vasculitis. All patients had cutaneous vasculitis and cryoglobulinemia. None of our patients had cirrhosis, yet three of the six patients died. Because of the severe manifestations, aggressive therapy was instituted with interferon, immunosuppressive medications, i.v. immunoglobulin, and plasmapheresis. Our report underscores the importance of recognizing nonhepatic manifestations in patients with hepatitis C infection that may be associated with high morbidity and mortality.

Adult↗
PubMed2001

Mushroom poisoning--from diarrhea to liver transplantation.

Mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common species. The typical symptoms of nausea, vomiting, abdominal pain, and diarrhea are nonspecific and can be mistaken for gastroenteritis. If not adequately treated, hepatic and renal failure may ensue within several days of ingestion. In this case series, patients poisoned with Amanita virosa are described with a spectrum of clinical presentations and outcomes ranging from complete recovery to fulminant hepatic failure. Although there are no controlled clinical trials, a few anecdotal studies provide the basis for regimens recommended to treat Amanita poisoning. Use of i.v. penicillin G is supported by most reports. Silibinin, although preferred over penicillin, is not easily available in the United States. In those with acute liver failure, liver transplantation can be life saving.

Adult↗
PubMed2001

Predictors of mortality and resource utilization in cirrhotic patients admitted to the medical ICU.

BACKGROUND AND OBJECTIVE: Cirrhotic patients admitted to the medical ICU (MICU) are associated with high mortality rates and high resource utilization. This study identifies specific predictors of increased mortality and resource utilization and uses them to develop and validate prognostic models in cirrhotic patients admitted to the MICU. METHODS: Cirrhotic patients admitted to the MICU were identified from the Critical Care Section database (January 1993 to October 1998). Clinical data were extracted from chart review including hospital course variables, mortality, and length of stay (LOS). Total cost per case (TCPC) was obtained from the Transition System INC: Multivariate logistic and linear regression analyses identified the independent predictors of increased mortality and resource utilization used for model building (MB) and model validation (MV). RESULTS: A total of 582 cases were randomized to the MB and MV groups. Each group contained 240 cases after exclusion criteria were applied. The MICU mortality rate was 36.6%, and the in-hospital mortality rate was 49.0%. Acute physiology, age, and chronic health evaluation (APACHE) III score (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.70 to 8.16; p < 0.001), mechanical ventilation (OR, 4.57; 95% CI, 2.35 to 8.34); p < 0.001), and the use of pressors (OR, 7.57; 95% CI, 4.35 to 13.18; p < 0.001) were independent predictors of MICU mortality. APACHE III score (OR, 4.96; 95% CI, 2.97 to 8.29; p < 0.001), the use of pressors (OR, 6.55; 95% CI, 3.66 to 11.72; p < 0.001), and acute renal failure (ARF) (OR, 4.31; 95% CI, 2.41 to 7.71; p < 0.001) were independent predictors of in-hospital mortality. Increased LOS in the MICU was associated with mechanical ventilation, ARF, bronchoscopy, bacteremia, use of pressors, transjugular intrahepatic portosystemic shunt (TIPS), and never received cardiopulmonary resuscitation (CPR) (p < 0.005). Source of admission, platelet transfusion, bacteremia, pneumonia, and never received CPR were independently associated with increased total LOS (p < 0.001). Mechanical ventilation, platelet transfusion, bronchoscopy, TIPS, sepsis, and never received CPR were independent predictors of increased TCPC (p < 0.001). CONCLUSION: Simple prognostic models for mortality and resource utilization have been developed for cirrhotic patients admitted to the MICU.

APACHE↗