To the best of our knowledge, the present study is the first to investigate LC in Israel with a focus on the AB population.
LC is one of the most frequent causes of death in Europe and the Middle East; however, it ranks low on the list of causes of mortality in Israel [3,8].
In the past three decades, the AB of southern Israel have undergone a major shift in lifestyle. This transition from a seminomadic to Western lifestyle makes this population of special interest, relevant to research on other minorities worldwide.
One of the important findings of our research is the frequency of LC among AB, 8.4% of all patients in the cohort. This percentage is much lower than that of the AB in the general population in southern Israel, which is about 33% . Our data showed a significantly lower rate of incidence of cirrhosis among AB compared with the incidence rate among the Jewish population during the follow-up time of the study. The low incidence may be specific to the Bedouin population of southern Israel due to their unique characteristics, while the incidence among the Jewish patients of southern Israel are largely representative of the general Israeli population.
Given the young average age of the AB (about 59% of the Arabs are younger than age 19 years) , rates of cirrhosis might be expected to be low. However, it has also been suggested that it is the low frequency of hepatitis C and alcohol liver disease among AB—generally the most common causes of cirrhosis—that may explain this low prevalence. Currently, since the approval of the direct-acting antivirals (DAA) for hepatitis C treatment with a sustained viral clearance of over 95% , the division of cirrhosis etiologies is likely to change in most countries. Hepatitis C may no longer be considered the main cause for cirrhosis. Rather, NAFLD, with its increasing incidence and no promising effective treatment on the horizon, as well as hepatitis B that is on the rise in some regions, are projected to climb higher on the list of common causes of cirrhosis in the near future. Both etiologies are responsible for many cases of cirrhosis in the AB in southern Israel.
NAFLD has been shown to be associated with obesity in the literature, with 80% of NAFLD patients being obese [13,14].The rates of obesity in the Arab population in Israel are higher than that of the Jewish population; 19.8% of Arab men and 24.3% of Arab women are obese, while the rates among Jews are 18% and 16%, respectively . Obesity in the AB age groups of 45–44, 55–64 and 65+ years are 34%, 47% and 45%, respectively. The rates among women are higher, up to 60% in some age groups . Older studies have shown that 29.9% of AB women overall are obese and 42% are overweight based on pre-pregnancy body mass index [17,18].
Given that obesity and hepatitis B are on the rise and that population in growing older, we project an increase in rates of LC among AB in the coming decades.
In contrast to the results of the present study regarding causes of cirrhosis, there are notable disparities in etiology between AB and Jewish patients. We observed that the most common causes of cirrhosis among AB patients were cryptogenic, hepatitis B, autoimmune hepatitis and NAFLD, while cases in Jewish patients were mainly derived from hepatitis C, NAFLD, alcoholic liver disease, and hepatitis B. In contrast with our results, studies in other countries mostly attributed alcoholic liver disease, NAFLD and hepatitis C to the development of cirrhosis [19,20].
In the Middle East, the most common factors leading to LC are hepatitis B and hepatitis C, with the highest prevalence of hepatitis C in Egypt (14%) [3–5].
When focusing on clinical characteristics, we find that a large proportion of AB patients with cirrhosis were female, (64% compared to 37% of Jewish patients), and the AB patients were significantly younger at the time of diagnosis (by an average of twenty years). These findings are possibly related to the etiology, since cryptogenic and autoimmune hepatitis are more common among females , while hepatitis C, alcoholic liver disease and NAFLD are more common in males.
Our data also show that more AB patients underwent liver biopsy than Jewish patients (42% versus 27%), which may stem from the etiology of the cirrhosis. A large portion of AB was diagnosed with cryptogenic or autoimmune hepatitis, and liver biopsies are necessary to formulate a complete and accurate diagnosis in these cases; such diagnostic methods are utilized less often in patients with hepatitis C or alcoholic liver disease.
Cryptogenic cirrhosis still high among AB patients, part of the patients underwent liver biopsy and some of the didn’t, however in these patients no cause for LC were found, but non alcoholic steatohepatitis still in the differential diagnosis, which is not diagnosed in the liver biopsy due to the advanced liver disease.
Notably, AB patients were diagnosed at a younger age, but had more esophageal varices, more bleeding esophageal varices, and more liver transplantations. There is no clear explanation for this finding; however, the younger age at diagnosis with poorer adherence to follow-up and treatment during the compensation period of the cirrhosis might be a risk factor for accelerated disease progression.
We found no differences in HCC and SBP. Approximately 13% of cirrhotic patients developed HCC in the two groups. Patients with LC have an increased risk for development of HCC and depending on the etiology and risk factors, the risk for HCC can reach 24% [22–24].
In the present study, the all-cause mortality among Jewish cirrhosis patients was significantly higher than in AB patients (63.4% compared to 41.8%, respectively). In our study, 61% of all cirrhosis patients died throughout the follow-up time, a relatively high mortality rate.
Fleming et al. estimated a hazard ratio (HR) of 4.7 for death among patients with compensated cirrhosis and 9.7 among patients with decompensated cirrhosis compared to the general population .
Mortality from LC in 2010 was estimated to be approximately 1 million worldwide, a significant global health burden .This burden has variable geographic distribution due do the differenced in the predominant etiologies of cirrhosis in each country.
The survival rate of our cohort estimated to be higher among AB, about 30% in a follow-up after 15 years, compared to 20% among Jewish patients.
However, the primary clinical outcomes defined in this study were significantly higher among Jewish patients than AB patients (67.9% and 49.3%, respectively), 608 versus 46 events.
Focusing on laboratory results, some laboratory values were abnormal as expected in both groups, including hemoglobin, platelets, liver enzymes, bilirubin, albumin and INR. A Child-Pugh score of 6 was assigned at diagnosis (Child A) and the last score was 7 and 8 (Child B) among AB and Jewish patients, respectively.
Despite the discrepancies between the two groups regarding clinical characteristics and outcomes, no significant differences were found in the laboratory results. Importantly, 58% of AB patients had normal ALT levels and 38% had normal AST levels. However, as calculated in table 2, the standard deviation of AST was relatively high (1200), which could be related to the high AST levels (up to 7000) among several AB patients recorded during previous hospitalizations. These high levels may be attributed to acute exacerbation or complication of the disease.
In summary, to the best of our knowledge this is the first study in Israel investigating cirrhosis in Bedouins in southern Israel. The strength of our study is in the large sample of cirrhosis patients, the findings of the study showed huge disparities among the AB patients compared with the Jewish patients. AB were diagnosed on average at a younger age, died at a younger age, and underwent more transplantations. Yet these AB patients still had a lower all-cause mortality and better survival rates, possibly due to cirrhosis etiology, time of diagnosis, and the seeking of medical services.
There are some limitations of the present study: first, the retrospective design of the study, and second, the incomplete data on treatment, hospitalization and precise causes of death.