Higher Incidence Of Cirrhosis Research Articles

THU-422 - PNPLA3 GG genotype is associated with higher incidence of cirrhosis and liver-related events among patients with non-alcoholic fatty liver disease

THU-422 - PNPLA3 GG genotype is associated with higher incidence of cirrhosis and liver-related events among patients with non-alcoholic fatty liver disease

Comment on: Textbook Outcomes Following Open Live Donor Right Hepatectomy and Open Right Hepatic Lobectomy for Cancer in 686 Patients: Re-Defining the Benchmark.

We read the article by Dogeas et al1 with great interest. This study used a prospective database to compare textbook outcomes (TO) rates between right hepatectomy (RH) for live donor purposes and RH for malignancy. The author found that the TO rates of RH for live donor purposes (92.2%) were significantly higher than that for malignancy (53.7%) and considered that these indicators represented a new benchmark for “real world” TO after open RH. Despite inspiring and thought-provoking, we have the following comments. First, in our experience, in the real world, regardless of the type of hepatectomy, the most common cause is hepatocellular carcinoma. However, among cancer patients in this study, the most common pathology was colorectal cancer liver metastases, accounting for 58.4% (184 patients). This also means that cirrhosis has a very low proportion of cancer patients, only 5.4% (17 patients). In fact, there may be a higher incidence of cirrhosis in all cancer patients who underwent RH. Although cirrhosis was only confirmed as an independent risk factor associated with a lower TO rate of hepatocellular carcinoma hepatectomy in our previous study,2 we still believe that cirrhosis may strongly affect the TO rate in all cases of hepatectomy. Therefore, it is reasonable to wonder whether the TO rate in the tumor patients in this study can be viewed as a new benchmark for the “real world” and whether independent factors associated with not achieving TO can be applied to all RH cancer patients. Second, this study noted that the live donor RH people had higher TO rates, as they were younger, healthier, and thinner, but logistic regression analysis showed no significant association between body mass index (BMI) and TO rates. The study did not mention the grouping method of BMI in the methods section. If BMI is analyzed as a continuous variable, it is likely to obtain negative results that BMI is not related to TO rates. However, high BMI often means that body obesity, while low BMI means body malnutrition or cachexia. Consequently, appropriate BMI grouping may directly determine the results of the study. We wanted to know how the authors analyzed of the association between BMI and TO rates. Third, TO rates were compared between RH for live donor purposes and RH for malignancy in this study. However, direct comparisons between the 2 groups may not be statistically appropriate due to the large difference between the 2 groups. Therefore, we believe that some statistical methods, such as propensity score matching or inverse probability of treatment weighting, should be used first to balance the baseline data between the 2 groups, perhaps to make the 2 groups more comparable. Although balancing may not have changed the final results of this study, we still believe that balancing the baselines of the 2 groups and then comparing them can make the results of this study more solid. Finally, we are still very appreciative of Dogeas et al1 for the new benchmark for “real world” TO after RH. We hold the belief that these findings will contribute to the further improvement and development of liver surgery.

Hepatitis B virus genetic multiplicity and the associated HBV lamivudine resistance mutations in HBV/HIV co-infection in Western Kenya: A review article.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infections are common as the two viruses use same routes of transmission. Studies show that HIV infection modifies the natural course of chronic HBV infection, leading to more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Therefore, determining HBV status and genotypes among HIV co-infected patients would improve their therapeutic management. This article reviewed the HBV genetic multiplicity and the associated HBV Lamivudine resistance mutations in HBV/HIV co-infection in western Kenya. Comprehensive literature searches and analysis were performed in peer-reviewed journals in the National council for biotechnology information (NCBI), PubMed, and Web of science using key words of HIV, Hepatitis B genotypes, HBV/HIV co-infection and Lamivudine resistance. HBV genotype A is predominant. D and E are also present in Kenya and neighboring countries in the region. HBV polymerase rtV173L, rtL180M, and rtM204V major substitutional mutations were identified. Currently, TDF+3TC+DTG are recommended for treatment of HBV/HIV co-infection. Evidence shows that HBV/HIV co-infection places a heavy burden to the society. Along with ART regimen, HBV genotype is a major factor determining the course of disease and treatment outcome. Treating HIV in HBV/HIV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistance mutations. Therefore, improved screening for HBV and extended follow-up of HBV/HIV co-infected individuals is needed to better understand the impact of different ART regimens on clinical outcomes.

Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon.

BackgroundHBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management. We conducted this study to understand the serologic and genotypic characteristics of HBV among HIV/HBV infected patients in South West and Littoral Regions of Cameroon.MethodsPlasma samples were screened for HBsAg, HBeAg, Anti-HBs and anti-HBc using ELISA followed by DNA extraction from all HBsAg positive samples. A 366 bp region covering the overlapping surface/polymerase gene was amplified by a nested PCR and the product sequenced using Big Dye sequencing chemistry. The resulting sequences were then analyzed for genotypes and both escape and drug resistance mutations.ResultsOf the 455 samples in this study, 25.5 % (n = 116) were HBsAg positive and 46 of these had their DNA successfully amplified. Genotype E was found in 32 samples (69.6 %) and genotype A in the rest of the samples. Escape mutations associated with failure of diagnosis (Y100C, R122K and Q129H) and with vaccine escape (Q129R and T131N) were detected in varying frequencies in the population. Polymerase mutations implicated in resistance to lamivudine and other ʟ-nucleoside analogues were detected in seven patients (15.2 %), while all the samples lacked mutations associated with resistance to adefovir and tenofovir.ConclusionsThese findings suggest the endemicity of HBV and the predominance of genotypes A and E in the study population. Also, drug resistance findings support the use of tenofovir based ART regimens among HIV/HBV co-infected persons. There is need for continuous HBV screening and monitoring in HIV infected individuals in these regions.

Laparoscopic left hemihepatectomy a consideration for acceptance as standard of care

Since the inception of laparoscopic liver surgery, the left-lateral sectionectomy has become the standard of care for resection of lesions located in segments II and III. However, few centers employee laparoscopic left hemihepatectomy on a routine basis. This study evaluated the safety and efficacy of the laparoscopic left hemihepatectomy as a standard of care. An international database of 1,620 laparoscopic liver resections was established and outcomes analyzed comparing the laparoscopic left lateral sectionectomy (L lat) to laparoscopic left hemihepatectomy (LH). All data are presented as mean ± standard deviation. A total of 222 laparoscopic L lat and 82 LH were identified. The L lat group compared with LH group had a higher incidence of cirrhosis (27 vs. 21 %; p = 0.003) and cancer (48 vs. 35 %; p = 0.043). Tumors were larger in the LH group (7.09 ± 4.2 vs. 4.89 ± 3.1 cm; p = 0.001). Operating time for LH was longer than L lat (3.9 ± 2.3 vs. 2.9 ± 1.4 h; p < 0.001). Operative blood loss was higher in LH (306 vs. 198 cc; p = 0.003). Patient morbidity (20 vs. 18 %; p = 0.765) was equivalent with a longer length of stay (7.1 ± 5.1 vs. 2.5 ± 2.3 days; p < 0.001) for LH. Patient mortality and tumor recurrence were equivalent. Laparoscopic left hemihepatectomy is a more technically challenging and often time-consuming procedure than a left-lateral sectionectomy. This international multi-institutional confirmed that intraoperative blood loss, complications, and conversions are more than acceptable for laparoscopic left hemihepatectomy in expert hands. Postoperative morbidity and mortality rates together with adequate surgical margins and long-term recurrence are not compromised by the laparoscopic approach.

Clinical characteristics of 638 patients infected with hepatitis C virus by post blood transfusion, in Shanghai

To investigate the clinical-epidemiologic characteristics of patients with hepatitis C virus (HCV) infection by post blood transfusion. Polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect HCV RNA and anti-HCV, respectively. Analysis was performed on patients' age distribution, cause of primary diseases, years of exposure, ingredient and amount of transfusion, incubation period, disorder on liver function and changes on abdominal ultrasound image, etc. HCV RNA levels were higher than 3.0 log(10) copy/ml in 90.8% infected patients with a median as 6.10 log(10) copy/ml. 19.2% of the patients showed viral load 3.0 to 4.0 log(10) copy/ml, and 66.1% of them showed 5.0 to 6.0 log(10) copy/ml. Only 14.7% of the infected persons had HCV RNA levels higher than 7.0 log(10) copy/ml. Eighty-one point five percent (44/54) of the infected persons were confirmed as HCV RNA positive by HCV RNA qualitative analysis with HCV genotype as primarily type 1. 99.8% (636/637) of the patients were detected as anti-HCV positive by serological test. The sensitivity of serological test was higher than both quantitative and qualitative HCV RNA assays (P = 0.000, P = 0.000, respectively). HCV infection post blood transfusion was more seen in common people at 40 to 60 years old. Most cases (85.7%) had their first exposure during 1990 to 1994. More than 10% of the cases had primary diseases as obstetrics, orthopedics or gastrointestinal tract hemorrhage. 79.9% of the patients received whole blood product transfusion. The mean interval between transfusion and clinical diagnosis was 8.5 ± 5.5 years. 90.1% of the infected patients had liver function damage, while most of them showed elevated alanine aminotransferase (ALT) no more than 5 upper limits of normal (ULN), whereas Serum total bilirubin (TBIL), ALT and aspartate aminotransferase (AST) ≥ 5 × ULN level were showing more clinical manifestations (P = 0.000, P = 0.001, P = 0.009, respectively). Abdominal ultrasound among 8.9% of the infected persons showed changes in cirrhosis, and most of them were older than 50 years of age. Most of the post transfusion HCV infected cases happened in adulthood, and were mainly exposed during 1990 to 1994. Infected patients usually had their liver function damaged with elevated ALT no more than 5 × ULN and with medium HCV RNA levels. HCV genotype was mainly for type 1. Patients who were of older age showed higher incidence of cirrhosis. If a patients' infection period was longer than 5 years, he/she would show higher incidence of cirrhosis.

S1917 Clinical Presentation and the Risks for a Higher Incidence of Cirrhosis and/or Hepatic Decompensation in Elderly Patients With Chronic Liver Diseases (CLD)

S1917 Clinical Presentation and the Risks for a Higher Incidence of Cirrhosis and/or Hepatic Decompensation in Elderly Patients With Chronic Liver Diseases (CLD)

The Natural History of Chronic HBV Infection and Geographical Differences

Although chronic HBV infection is a global health issue, there are geographical differences in the mode of transmission, prevalence and HBV genotype distribution. Chronic HBV infection is a dynamic state of interactions between HBV, hepatocytes and immune cells of the host. Accordingly, the natural history of chronic HBV infection typically starts with an immune tolerant phase, followed by an immune clearance phase and finally an inactive phase. The duration of the immune tolerant phase is usually long in chronic HBV infection acquired perinatally or in early childhood, otherwise the duration is very short. During the inactive phase, spontaneous hepatitis B surface antigen (HBsAg) seroclearance might occur at an annual rate of 1-2%; however, HBV reactivation with hepatitis activity could occur over time in one-quarter to one-third of HBsAg-seropositive patients. This occurs more frequently in males and in patients infected with genotypes D, C and B. The effort of active HBV replication-triggered immune clearance is the driving force of liver injury and subsequent disease progression in patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative hepatitis. Clinical studies have shown that chronic HBV infection in western countries is associated with a higher incidence of cirrhosis, but lower incidence of hepatocellular carcinoma, than in Asian countries. The geographical differences in age at the time of infection and predominant HBV genotype could account for the variance in the natural history of chronic HBV infection; however, some of these differences might actually result from comparisons between cohorts with different age, gender distribution or fibrosis stage.

Cytokines and liver injury in chronic HCV genotype 4 infection

Cytokines and liver injury in chronic HCV genotype 4 infection

Natural Course, Therapeutic Options and Economic Evaluation of Therapies for Chronic Hepatitis B

Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.

Anemia in the treatment of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a significant worldwide health care problem. Nearly one-third of all patients infected with human immunodeficiency virus (HIV) are coinfected with HCV. Compared with HIV-monoinfected persons, coinfected individuals experience more rapid progression of fibrosis and higher incidence of cirrhosis and death as a result of liver disease. Treatment for HCV infection includes ribavirin (RBV) plus interferon alfa (IFN-alpha) or pegylated IFN, a combination treatment associated with anemia that may require RBV dose reduction or discontinuation. IFN-RBV-associated anemia is more profound among coinfected patients, who have a high prevalence of pretreatment anemia and may also be taking other medications causing anemia. Epoetin alfa administration to HCV-infected patients with IFN-RBV-related anemia can significantly increase hemoglobin levels and maintain significantly higher RBV doses compared with patients treated with RBV dose reduction alone. Higher RBV doses and adherence to HCV therapy have been associated with higher sustained virologic response (SVR) rates. Maintenance of RBV dose with epoetin alfa may improve adherence, thereby affecting SVR.

Investigation of alcohol metabolizing enzyme genes in Chinese alcoholics with avascular necrosis of hip joint, pancreatitis and cirrhosis of the liver.

Alcoholism may cause a range of diseases including avascular necrosis of the hip joint (AVN), cirrhosis of the liver, pancreatitis and oesophageal carcinoma. Chinese alcoholic patients diagnosed with AVN have a higher incidence of cirrhosis than of acute pancreatitis or oesophageal cancer. Thus, the aim of this study was to investigate genetic differences in polymorphisms of the alcohol-metabolizing enzymes ADH2, ADH3, ALDH2 and P4502E1 for subgroups of Chinese alcoholic patients, defined by diagnoses of AVN (n = 51), acute pancreatitis (n = 92) and liver cirrhosis (n = 159), and for 280 non-alcoholic patients. Analysis revealed that ADH2*1 allele frequency was significantly lower for the alcoholic AVN than for the cirrhosis subgroup. However, no significant difference was found between the alcoholic AVN and pancreatitis subgroups. Furthermore, ALDH2*2 prevalence was not found to differ significantly between the alcoholic subgroups. When compared with our previously published data for alcoholic patients with oesophageal carcinoma, ADH2*1 carriage was significantly less frequent for the alcoholic AVN patients in the current study. Further, ALDH2*2 carriage was significantly less frequent for the alcoholic AVN subgroup than for the oesophageal carcinoma patients. The allele frequencies for ADH2*1 and ALDH2*2 are different when comparing subpopulations of alcoholics defined by presence of specific alcohol-induced diseases, suggesting that genetic variation in alcohol-metabolizing enzyme genes accounts for, at least in part, the specific types of organ damage observed. We also found the combination of AVN and cirrhosis to be more prevalent than that of AVN and acute pancreatitis. In contrast, the ADH2 and ALDH2 allele frequencies for the AVN subgroup were more similar to those of the acute-pancreatitis than to the cirrhosis subgroup. These data indicate the possibility that other genetic variations may also influence the type of organ-specific complications in Chinese alcoholics.

Outcome of orthotopic liver transplantation in autoimmune hepatitis according to subtypes.

The relevance of autoimmune hepatitis (AIH) classification for clinical purposes is controversial. We analyzed the outcome after orthotopic liver transplantation (OLT) of nine type I and seven type II AIH patients. Type II patients had a significantly higher incidence of cirrhosis at the time of diagnosis, more resistance to steroid therapy, and a higher Child-Pugh score at the time of OLT. OLT was performed in emergency in three type II patients and electively in all type I patients. Four type II and one type I patients died in the postoperative period. There was no difference regarding the incidence of post-OLT infection and rejection between the two types. No recurrence of AIH was observed. The 6-year actuarial survival rates for type I and type II patients were 76% and 43%, respectively. Type II AIH patients who have a poor response to medical therapy should be considered for OLT with a shortened delay.

Clinical, virological and histopathological features: long‐term follow‐up in patients with chronic hepatitis C co‐infected with S. mansoni

Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7 +/- 22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13 x 10(5) copies/ml in group A, and between 1 and 25 x 10(5) copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.

Cryoglobulinemia in hepatitis C virus chronic active hepatitis: effects of interferon-alpha therapy.

We investigated the prevalence of mixed cryoglobulinemia (MC) in 100 cases of chronic hepatitis C virus (HCV) infection and the effect of a 6-month treatment with interferon-alpha (IFN-alpha). Cryoglobulins were detected on admission in 36 of 100 patients and appeared during observation in a further 18 cases. Cryocrit ranged from 0.5% to 20%. Patients with MC were older and had a higher incidence of cirrhosis than those without MC. Immunologic characterization of the cryoprecipitate showed the presence of type II in 84% of cases and type III in 16%. The patients received IFN-alpha (6 MU three times per week) for 6 months. Fifty-seven were responders (i.e., reached normal aminotransferase levels), 26 of these relapsed within 2 months after IFN withdrawal, and 30 did not relapse. After IFN-alpha treatment, cryoglobulinemia disappeared in 11 of the 21 evaluable responders, but in none of the 15 nonresponder patients (p < 0.003). The clearance of MC was associated in all cases with clearance of HCV RNA. The delayed appearance of cryoglobulinemia in responders seems to be associated with a higher probability of relapse.