Sabahattin Kaymakoglu

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Tuberculous peritonitis--reports of 26 cases, detailing diagnostic and therapeutic problems.

Objective To evaluate the clinical presentation, biochemical (ascites and serum) and laparoscopic findings, and to assess the efficacy of triple anti-tuberculous therapy without rifampicin for 6 months in patients with tuberculous peritonitis. Methods Twenty-six tuberculous peritonitis patients (11 male, 15 female) with a mean age of 34.8 ± 3.4 years (range 14–77) were assessed with regard to diagnostic and therapeutic features. Results The most common symptoms and signs were abdominal pain (92.3%) and ascites (96.2%), respectively. Tuberculin skin test (TST) was positive in all patients. An abnormal chest radiography suggestive of previous tuberculosis was present in five patients (19.2%), and two patients (7.7%) had extra-peritoneal (cerebral, pericardial) active tuberculous involvement. In 24 of the 25 patients who underwent laparoscopy with directed biopsy, whitish nodules suggested tuberculous peritonitis; 76% of the biopsy specimens revealed caseating, 20% non-caseating granulomatous inflammation, and 4% non-specific findings. The ascitic fluid of one patient (3.8%) was positive for acid-resistant bacilli, and culture was positive in two patients (7.7%). Twenty-four of the patients were treated for 6 months with isoniazid, streptomycin (total dose 40 g) and pyrazinamide (for the first 2 months and then substituted with ethambutol). Eighteen patients also received methyl prednisolone, initially 20 mg/day, for 1 month. The follow-up period was 19 ± 1.7 months after the end of therapy (range 6–36). Ascites and abdominal pain abated earlier in patients on steroid therapy. All but two of the 24 patients responded to treatment. Conclusion Non-invasive tests such as acid-fast stain and culture of the ascitic fluid are usually insufficient, hence invasive laparoscopy and peritoneal biopsy are necessary for the diagnosis of tuberculous peritonitis if non-invasive tests such as ascites adenosine deaminase activity measurement are not easily available. Triple therapy without rifampicin for 6 months is sufficient to treat tuberculous peritonitis.

Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection.

BACKGROUND/AIMS End-stage renal disease patients on chronic hemodialysis are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Although the prevalence is unknown in hemodialysis patients, occult HBV infection is frequent in subjects with chronic HCV infection. We aimed to investigate (1) the prevalence and clinical impact of occult HBV infection in hemodialysis patients with chronic HCV infection, and (2) the frequency of YMDD variants (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) in this setting. METHODS Thirty-three anti-HCV and HCV-RNA-positive, HBsAg-negative hemodialysis patients (mean age 36.9+/-10.4 years, 22 male) were admitted to this study. HBV-DNA (Innogenetics kit) and HCV-RNA (Cobas Amplicor HCV kit) were investigated by polymerase chain reaction technique (PCR). YMDD mutation was studied in all HBV-DNA-positive patients by the BOOM method. RESULTS HBV-DNA was detected in 12 of 33 patients (36.4%) by PCR. Their mean age was 33.0+/-9.0 years. Age, dialysis period (years) and biochemical parameters were not significantly different in patients with and without occult HBV infection. YMDD variants were identified in six of 12 (50%) patients with occult HBV infection. CONCLUSIONS Occult HBV infection is frequent in hemodialysis patients with chronic HCV infection. YMDD variants are common in this setting.

Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients.

Hepatopulmonary syndrome has yet not been sufficiently assessed in noncirrhotic portal hypertension. The prevalence of hepatopulmonary syndrome was determined in 31 consecutive patients with noncirrhotic portal hypertension (19 idiopathic portal hypertension, 7 portal vein thrombosis, 5 congenital hepatic fibrosis) and 46 patients with liver cirrhosis. Contrast echocardiography was carried out in all patients. Macroaggregated albumin lung perfusion scans were performed in patients with positive contrast echocardiogram. Hepatopulmonary syndrome was detected in 5 (10.8%) cirrhotic and 3 (9.7%) noncirrhotic portal hypertensive patients (2 idiopathic portal hypertension, 1 portal vein thrombosis). All patients with hepatopulmonary syndrome had an increased shunt fraction (13–62%) and a decreased diffusion capacity of carbon monoxide (40–79%), and 7 of them were hypoxemic (PaO2, 31.6–69.8 mm Hg). These findings show that hepatopulmonary syndrome may occur in both liver cirrhosis and noncirrhotic portal hypertension and that portal hypertension is the predominant etiopathogenic factor related to hepatopulmonary syndrome.

Is severe cryptogenic chronic hepatitis similar to autoimmune hepatitis

BACKGROUND/AIMS It has been reported that severe cryptogenic chronic hepatitis may be a subgroup of autoimmune hepatitis. The aims of this study were to investigate the clinical features, liver function tests, human leukocyte antigens and response to immunosuppressive therapy in severe cryptogenic chronic hepatitis, and to compare the findings in such patients with those in patients with autoimmune hepatitis. METHODS History of alcohol and hepatotoxic drug intake, markers of metabolic liver disease, autoantibodies (antinuclear antibody, smooth muscle antibody, antibody to liver/kidney microsome type 1), and viral markers (HBsAg, HBV DNA, anti-HCV, HCV RNA) were negative in all severe cryptogenic chronic hepatitis patients (histological activity index > 9 and alanine aminotransferase level > 2 x normal). Fifteen cryptogenic patients (13 women; mean age, 33 +/- 16 years) and seven autoimmune patients (seven women; mean age, 28 +/- 3.9 years; five type 1; two type 2a) received prednisolone and azathioprine for at least 2 years. RESULTS Cryptogenic chronic hepatitis patients were similar to patients with autoimmune hepatitis with respect to age, sex, clinical presentation, liver function tests and Knodell scores at admission. HLA phenotype frequencies were comparable between cryptogenic and autoimmune groups: BW6 (77% vs. 100%), DR4 (62% vs. 57%), and HLA B8 (15% vs. 43%). The rates of complete and partial remissions achieved during therapy were 87% vs. 57% and 13% vs. 29%, respectively (p > 0.05). CONCLUSIONS The clinical, biochemical and HLA phenotypic features, and the responsiveness to immunosuppressive therapy in severe cryptogenic chronic hepatitis support the idea that it may be an autoimmune liver disease similar to autoimmune hepatitis.

Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma

Abstract In this study, two cases of biopsy‐proven pancreatic tuberculosis are reported. The patients presented with fever, anorexia, fatigue, abdominal pain and weight loss. A differential diagnosis of fever of unknown origin was conducted. Computed tomography (CT) revealed a cystic mass image in the pancreatic head in one patient, and a hypodense lesion in the pancreatic head in the other. The first patient was diagnosed by a wedge biopsy specimen obtained in the exploratory laparotomy. The other patient was diagnosed by percutaneous fine‐needle aspiration biopsy. Both patients were successfully treated with quadruple antituberculous therapy for 12 months. We concluded that especially in young patients who present with a mass in the pancreas, pancreatic tuberculosis should be considered among the differential diagnoses, particularly in developing countries and immunosuppressed individuals.

Efficacy of Tenofovir in Patients with Lamivudine Failure Is Not Different from That in Nucleoside/Nucleotide Analogue-Naïve Patients with Chronic Hepatitis B

ABSTRACT We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

Are Acquired Hepatocerebral Degeneration and Hepatic Myelopathy Reversible

Background Acquired hepatocerebral degeneration (AHD) and hepatic myelopathy (HM) are rare complications of chronic liver disease and are usually resistant to medical therapy. Materials and Methods The clinical and laboratory findings of 14 male and 2 female patients with AHD or HM were evaluated. Results The prevalence of AHD and HM was 2% inpatient case series in the last 10 years. The median age of the patients (5 Childs B and 11 Childs C) was 48.7 years (28 to 66 y), and the mean known duration of the liver disease was 75 months (24 to 194 mo). The median time of onset of neurologic findings after diagnosis of the liver disease was 14.5 months. Eight patients who had marked spastic paraparesis or tetraparesis were included in the HM group and all others had AHD group. Sixty-nine percent of the patients had a spontaneous or surgical portosystemic shunts, and the remaining dense retroperitoneal collaterals. During the follow-up period of median 29 months (4 to 72 mo), 12 patients died while waiting for liver transplantation, and these patients suffered from the several complications of chronic liver disease more than the living patients. A marked improvement was observed in 2 of the patients (1 with AHD and the other with HM) at 6 and 8 months after the liver transplantation, respectively. Conclusions Our data suggest that liver transplantation had an important effect on the improvement in these patients.

Alpha Interferon and Ribavirin Combination Therapy of Chronic Hepatitis D

ABSTRACT The success of alpha interferon (IFN-α) monotherapy for the treatment of chronic hepatitis D is very limited. In this study, the efficacy of IFN-α and ribavirin combination therapy for chronic hepatitis D was investigated. Nineteen patients (15 males; mean age ± standard deviation, 36.8 ± 12.8 years) with chronic hepatitis D who were treated with IFN-α2b (10 million U, three times/week, subcutaneously) and ribavirin (1,000 to 1,200 mg/day, orally) for 24 months were studied. All patients had compensated liver disease (15 were precirrhotic), elevated transaminase levels, and hepatitis D virus RNA positivity at baseline. Genotypic analyses revealed hepatitis D virus genotype I and hepatitis B virus genotype D. All patients completed the 24 months of treatment and at least 6 months (7 to 19 months) of a follow-up period. Biochemical responses were observed in eight patients (42.1%) at the end of treatment and in seven patients (36.8%) at the end of follow-up. Eight patients (42.1%) at the end of treatment and four patients (21%) at the end of follow-up had virological responses. In conclusion, combination treatment of IFN-α and ribavirin for chronic hepatitis D is not able to induce virological responses at a sufficient rate, despite its partial effectiveness in improving biochemical responses, and is not superior to IFN-α monotherapy.